Gen terapiyasi sahifasining manbasini koʻrish

{{Gen muhandisligi yon paneli}}
'''Gen terapiyasi''' — [[Gen ekspressiyasi|genlar ekspressiyasini]] oʻzgartirish yoki tirik hujayralarning biologik xususiyatlarini oʻzgartirish orqali [[Davolovchi ta’sir|davolovchi taʼsirga]] erishishni maqsad qilgan [[Sog‘liqni saqlash texnologiyalari|tibbiy texnologiya]]<ref>{{cite journal | vauthors = Kaji EH, Leiden JM | title = Gene and stem cell therapies | url = https://archive.org/details/sim_jama_2001-02-07_285_5/page/n56 | journal = JAMA | volume = 285 | issue = 5 | pages = 545–550 | date = February 2001 | pmid = 11176856 | doi = 10.1001/jama.285.5.545 | doi-access = free }}</ref><ref>{{cite book|title=Emerging Medical Technologies| vauthors = Ermak G | publisher=World Scientific|year=2015|isbn=978-981-4675-81-9}}</ref><ref>{{Cite web |date=9 December 2020 |title=What is Gene Therapy? |url=https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy |archive-url=https://web.archive.org/web/20190607231236/https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy |archive-date=7 June 2019 |publisher=U.S. [[Food and Drug Administration]] (FDA) }}</ref><ref>https://arxiv.org/pdf/2603.19473 Gene therapy foundations</ref>.

Inson [[DNK]]sini oʻzgartirish boʻyicha birinchi urinish 1980-yilda [[Martin Cline]] tomonidan amalga oshirilgan. Ammo insonlarda [[milliy sog‘liqni saqlash institutlari]] tomonidan maʼqullangan birinchi muvaffaqiyatli yadroviy gen koʻchirish 1989-yil may oyida amalga oshirildi<ref>{{cite journal | vauthors = Rosenberg SA, Aebersold P, Cornetta K, Kasid A, Morgan RA, Moen R, Karson EM, Lotze MT, Yang JC, Topalian SL | display-authors = 6 | title = Gene transfer into humans--immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction | url = https://archive.org/details/sim_new-england-journal-of-medicine_1990-08-30_323_9/page/570 | journal = The New England Journal of Medicine | volume = 323 | issue = 9 | pages = 570–578 | date = August 1990 | pmid = 2381442 | doi = 10.1056/NEJM199008303230904 | doi-access = free }}</ref>. Birinchi marta davolash maqsadida gen koʻchirish, shuningdek, inson DNKsini toʻgʻridan-toʻgʻri yadro genomiga kiritish amaliyoti 1990-yil sentabrdan boshlangan klinik sinovda [[French Anderson]] tomonidan bajarilgan. 1989-yildan 2018-yil dekabriga qadar 2900 dan ortiq klinik sinovlar oʻtkazilgan boʻlib, ularning yarmidan koʻpi [[Klinik tadqiqotlar bosqichlari|I fazada]] boʻlgan<ref name="JGenMed Database">{{cite web | url = http://www.abedia.com/wiley/phases.php | title = Gene Therapy Clinical Trials Worldwide Database | archive-url = https://web.archive.org/web/20200731222220/http://www.abedia.com/wiley/phases.php | archive-date=31 July 2020 | work = The Journal of Gene Medicine | publisher = Wiley | date = June 2016 }}</ref>. 2003-yilda „[[Gendicine]]“ rasmiy ruxsatnoma olgan dunyodagi birinchi gen terapiyasi dori vositasiga aylandi. Oʻshandan beri yana boshqa gen terapiyasi dori vositalari, jumladan, [[alipogene tiparvovec]] (2012), [[Strimvelis]] (2016), [[tisagenlecleucel]] (2017), [[voretigene neparvovec]] (2017), [[patisiran]] (2018), [[onasemnogene abeparvovec]] (2019), [[idecabtagene vicleucel]] (2021), [[nadofaragene firadenovec]], [[valoctocogene roxaparvovec]] va [[etranacogene dezaparvovec]] (barchasi 2022-yilda) maʼqullandi.

Koʻp hollarda gen terapiyasi yondashuvlarida genlarni kiritish amaliyotini bajarish uchun muvofiq ravishda in vivo hamda ex vivo usullari orqali adeno-[[assotsiatsiyalangan virus]]lar (AAV) va [[lentivirus]]lardan foydalanilgan. AAVlar virus kapsidini barqarorlashtirishi, past immunogenligi, ham boʻlinadigan, ham boʻlinmaydigan hujayralarni transduksiya qilish qobiliyati, maqsadli sohaga xos tarzda integratsiyalashuv salohiyati hamda in vivo davolashda uzoq muddatli ekspressiyaga erisha olishi bilan ajralib turadi<ref name = "Gorell_2014">{{cite journal | vauthors = Gorell E, Nguyen N, Lane A, Siprashvili Z | title = Gene therapy for skin diseases | journal = Cold Spring Harbor Perspectives in Medicine | volume = 4 | issue = 4 | article-number = a015149 | date = April 2014 | pmid = 24692191 | pmc = 3968787 | doi = 10.1101/cshperspect.a015149 }}
</ref>. [[Alnylam Pharmaceuticals|Alnylam]] va [[Ionis Pharmaceuticals]] tomonidan olib boriladiganlar kabi ASO / siRNA yondashuvlari virusli boʻlmagan yetkazib berish tizimlarini talab qiladi va [[N-Atsetilgalaktozamin|GalNAc]] transportyorlari vositasida jigar hujayralariga yetib borish uchun muqobil mexanizmlardan foydalanadi.

Bemorning genetik tuzilishiga oʻzgartirishlar kiritadigan har qanday tibbiy muolajani ham gen terapiyasi deb hisoblab boʻlmaydi. Masalan, [[suyak koʻmigi transplantatsiyasi]] va umuman [[Transplantatsiya|organ koʻchirib oʻtkazish]] amaliyotlari bemor organizmiga yot DNKni kiritishi aniqlangan<ref>{{cite news|title=DNA Double Take| vauthors = Zimmer C | date = 16 September 2013|work=The New York Times|url=https://www.nytimes.com/2013/09/17/science/dna-double-take.html |archive-url=https://ghostarchive.org/archive/20220102/https://www.nytimes.com/2013/09/17/science/dna-double-take.html |archive-date=2 January 2022 |url-access=limited |url-status=live }}</ref>.

== Tarixi ==
Gen terapiyasi konsepsiyasi birinchi marta 1960-yillarda, [[sutemizuvchi]]lar [[hujayra]]lariga yangi genetik funksiyalarni qoʻshish imkoniyatlarini tadqiq qilish boshlangan davrda paydo boʻlgan. Buning uchun bir qancha usullar, jumladan, mikropipetka yordamida genni toʻgʻridan-toʻgʻri tirik sutemizuvchi hujayrasiga kiritish va hujayralarni kerakli [[gen]]larni oʻz ichiga olgan DNK choʻkmasi taʼsirida qoldirish kabi usullar sinovdan oʻtkazildi. Olimlar viruslardan ham hujayralarga yangi genlarni yetkazib beruvchi vosita yoki vektor sifatida foydalanish mumkinligi haqidagi nazariyani ilgari surdilar.

Faoliyat koʻrsatayotgan [[DNK]]ning sutemizuvchi hujayrasiga toʻgʻridan-toʻgʻri va muvaffaqiyatli kiritilgani haqida birinchilardan boʻlib hisobot bergan olimlardan biri — [[Tennessi]] shtati [[Memphis (Tennessee)|Memfis]] shahridagi [[Tennessi universiteti sogʻliqni saqlash fanlari markazi]] [[biokimyogar]]i, doktor [[Lorraine Marquardt Kraus]] (1922-yil 6-sentabr — 2016-yil 1-iyul) boʻldi<ref name="The Commercial Appeal">{{cite web |title=Lorraine Kraus Obituary |url=https://www.legacy.com/us/obituaries/commercialappeal/name/lorraine-kraus-obituary?id=8890655 |website=The Commercial Appeal |access-date=7 July 2023}}</ref>. 1961-yilda u oʻroqsimon hujayrali kamqonlik bilan ogʻrigan bemorning suyak koʻmigidan olingan hujayralar gemoglobinini genetik jihatdan oʻzgartirishga muvaffaq boʻldi. U buni bemor hujayralarini toʻqima kulturasida normal gemoglobinga ega boʻlgan donordan ajratib olingan DNK bilan birga inkubatsiya qilish orqali amalga oshirdi. 1968-yilda [[AQSh]]ning Betesda shahridagi Milliy sogʻliqni saqlash institutlari tadqiqotchilari [[Theodore Friedmann]], [[Jay Seegmiller]] va [[John Subak-Sharpe]] ushbu kasallikdan aziyat chekayotgan bemorlardan olingan hujayralar kulturasiga yot DNK qoʻshish orqali ogʻir nevrologik xastalik — Lesch-Nyhan sindromi bilan bogʻliq genetik nuqsonlarni muvaffaqiyatli tuzatishga erishdilar<ref name="Biotechmet">{{cite web |title=Gene therapy |url=https://www.whatisbiotechnology.org/index.php/science/summary/gene-therapy/ |website=WhatIsBiotechnology.org |publisher=The Biotechnology and Medicine Education Trust (Biotechmet) |access-date=7 July 2023}}</ref>.

Gen terapiyasini qoʻllash boʻyicha birinchi hamda muvaffaqiyatsiz yakunlangan urinish (shuningdek, organ koʻchirib oʻtkazishni hisobga olmaganda, inson tanasiga yot genlarni tibbiy yoʻl bilan kiritish boʻyicha birinchi holat) 1980-yil 10-iyulda [[AQSh]]ning [[Kaliforniya]] shtatida, Los-Anjelesdagi Kaliforniya universiteti genetigi [[Martin Cline]] tomonidan amalga oshirildi<ref>{{cite book | title = Human gene therapy – A background paper | author = U.S. Congress, Office of Technology Assessment | publisher = DIANE Publishing | isbn = 978-1-4289-2371-3 | url = https://books.google.com/books?id=FxGjBqEL-3kC&pg=PA45 | date = December 1984 }}</ref><ref>{{cite journal | vauthors = Sun M | title = Martin Cline loses appeal on NIH grant | url = https://archive.org/details/sim_science_1982-10-01_218_4567/page/37 | journal = Science | volume = 218 | issue = 4567 | page = 37 | date = October 1982 | pmid = 7123214 | doi = 10.1126/science.7123214 | bibcode = 1982Sci...218...37S }}</ref>. Martin Cline bemorlaridagi genlardan biri olti oy oʻtgach ham faol boʻlganini daʼvo qilgan, biroq ushbu maʼlumotlarni hech qachon eʼlon qilmagan va tekshiruvdan oʻtkazmagan<ref>{{cite book | chapter-url = https://books.google.com/books?id=FzuwRwb--X4C&pg=PA30 | chapter = Gene Therapy for Neurological Disorders: New Therapies or Human Experimentation? | title = A Companion to Genethics | vauthors = Lowenstein PR | veditors = Burley J, Harris J | isbn = 978-0-470-75637-9 | publisher=John Wiley & Sons | year = 2008 }}</ref>.

1980-yillar davomida hayvonlar ustida olib borilgan keng koʻlamli tadqiqotlar va 1989-yilda insonlarda oʻtkazilgan bakterial genlarni markirovka qilish sinovidan soʻng, keng jamoatchilik tomonidan muvaffaqiyatli deb eʼtirof etilgan birinchi gen terapiyasi 1990-yil 14-sentabrda boshlangan [[klinik sinov]]da namoyish etildi. Unda [[Ashanthi DeSilva]] ADA-SCID (adenozindezaminaza yetishmovchiligi oqibatidagi ogʻir kombinatsiyalangan immun tanqisligi) kasalligidan davolangan edi<ref name="Gene Therapy Finds Its Niche">{{cite journal | vauthors = Sheridan C | title = Gene therapy finds its niche | url = https://archive.org/details/sim_nature-biotechnology_2011-02_29_2/page/121 | journal = Nature Biotechnology | volume = 29 | issue = 2 | pages = 121–128 | date = February 2011 | pmid = 21301435 | doi = 10.1038/nbt.1769 | s2cid = 5063701 }}</ref>.

Doimiy genetik oʻzgarishga olib kelgan birinchi somatik davolash usuli 1993-yilda boshlangan<ref>{{cite journal |vauthors=O'Malley BW, Ledley FD |title=Somatic gene therapy. Methods for the present and future |journal=Arch Otolaryngol Head Neck Surg |volume=119 |issue=10 |pages=1100–7 |date=October 1993 |pmid=8398061 |doi=10.1001/archotol.1993.01880220044007 }}</ref>. Bundan maqsad rekombinant DNK yordamida oʻsma hujayralarini dori vositasiga sezgir qiluvchi genni kiritish va oʻz navbatida, ushbu oʻsma hujayralarining nobud boʻlishini taʼminlash orqali xavfli miya oʻsmalarini davolash boʻlgan<ref>{{cite journal | vauthors = Oldfield EH, Ram Z, Culver KW, Blaese RM, DeVroom HL, Anderson WF | title = Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir | journal = Human Gene Therapy | volume = 4 | issue = 1 | pages = 39–69 | date = February 1993 | pmid = 8384892 | doi = 10.1089/hum.1993.4.1-39 }}</ref>.

Polimerlar esa yoki oqsillarga translyatsiya qilinadi, yoki maqsadli [[gen ekspressiyasi]]ga taʼsir koʻrsatadi, yoxud genetik [[mutatsiya]]larni tuzatishi mumkin. Eng keng tarqalgan shaklida mutatsiyaga uchragan genni almashtirish uchun funksional, terapevtik genni kodlovchi DNKdan foydalaniladi. Polimer molekulasi uni hujayralar ichiga olib kiruvchi maxsus „vektor“ ichiga joylashtiriladi.

Dastlabki klinik muvaffaqiyatsizliklar gen terapiyasiga boʻlgan qiziqishning soʻnishiga olib keldi. 2006-yildan boshlab erishilgan klinik yutuqlar tadqiqotchilar eʼtiborini yana bu sohaga qarata boshladi<ref name="Richards2012">{{cite web| vauthors = Richards S |title=Gene Therapy Arrives in Europe|url=http://www.the-scientist.com/?articles.view/articleNo/33166/title/Gene-Therapy-Arrives-in-Europe/|work=The Scientist|date=6 November 2012}}</ref><ref name="Gallagher">{{cite web | vauthors = Gallagher J | date = 2 November 2012 | url = https://www.bbc.co.uk/news/health-20179561 | title = Gene therapy: Glybera approved by European Commission | work = BBC News | access-date = 15 December 2012 }}</ref>. Lekin shunda ham 2014-yil holatiga koʻra, u hali ham asosan eksperimental usul boʻlib qolayotgan edi<ref name="Maguire 2008">{{cite journal | vauthors = Maguire AM, Simonelli F, Pierce EA, Pugh EN, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J | display-authors = 6 | title = Safety and efficacy of gene transfer for Leber's congenital amaurosis | journal = The New England Journal of Medicine | volume = 358 | issue = 21 | pages = 2240–2248 | date = May 2008 | pmid = 18441370 | pmc = 2829748 | doi = 10.1056/NEJMoa0802315 }}</ref><ref name="Simonelli 2010">{{cite journal | vauthors = Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM, Sun J, Redmond TM, Zhu X, Shindler KS, Ying GS, Ziviello C, Acerra C, Wright JF, McDonnell JW, High KA, Bennett J, Auricchio A | display-authors = 6 | title = Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration | journal = Molecular Therapy | volume = 18 | issue = 3 | pages = 643–650 | date = March 2010 | pmid = 19953081 | pmc = 2839440 | doi = 10.1038/mt.2009.277 }}</ref><ref name="Cideciyan 2009">{{cite journal | vauthors = Cideciyan AV, Hauswirth WW, Aleman TS, Kaushal S, Schwartz SB, Boye SL, Windsor EA, Conlon TJ, Sumaroka A, Roman AJ, Byrne BJ, Jacobson SG | title = Vision 1 year after gene therapy for Leber's congenital amaurosis | journal = The New England Journal of Medicine | volume = 361 | issue = 7 | pages = 725–727 | date = August 2009 | pmid = 19675341 | pmc = 2847775 | doi = 10.1056/NEJMc0903652 }}</ref><ref name="Bainbridge 2008">{{cite journal | vauthors = Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR | display-authors = 6 | title = Effect of gene therapy on visual function in Leber's congenital amaurosis | url = https://archive.org/details/sim_new-england-journal-of-medicine_2008-05-22_358_21/page/2231 | journal = The New England Journal of Medicine | volume = 358 | issue = 21 | pages = 2231–2239 | date = May 2008 | pmid = 18441371 | doi = 10.1056/NEJMoa0802268 | hdl = 10261/271174 | hdl-access = free }}</ref>. Ushbu yutuqlar qatoriga koʻz toʻr pardasi kasalliklaridan Leberning tugʻma amavrozi va [[xoroidiremiya]]<ref name="BBC2016">{{cite news| vauthors = Ghosh P |title=Gene therapy reverses sight loss and is long-lasting |url= https://www.bbc.co.uk/news/science-environment-36101786|access-date=29 April 2016|publisher=BBC News Online |date=28 April 2016 }}</ref>, [[X xromosoma]]siga bogʻliq SCID, ADA-SCID<ref>{{cite journal | vauthors = Fischer A, Hacein-Bey-Abina S, Cavazzana-Calvo M | title = 20 years of gene therapy for SCID | journal = Nature Immunology | volume = 11 | issue = 6 | pages = 457–460 | date = June 2010 | pmid = 20485269 | doi = 10.1038/ni0610-457 | s2cid = 11300348 }}</ref><ref>{{cite journal | vauthors = Ferrua F, Brigida I, Aiuti A | title = Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency | journal = Current Opinion in Allergy and Clinical Immunology | volume = 10 | issue = 6 | pages = 551–556 | date = December 2010 | pmid = 20966749 | doi = 10.1097/ACI.0b013e32833fea85 | s2cid = 205435278 }}</ref><ref name="NewScientist1013" />, adrenoleyko-distrofiya, surunkali limfotsitar leykemiya (SLL), oʻtkir limfotsitar leykemiya (OLL)<ref>{{cite journal | vauthors = Cartier N, Aubourg P | title = Hematopoietic stem cell transplantation and hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy | journal = Brain Pathology | volume = 20 | issue = 4 | pages = 857–862 | date = July 2010 | pmid = 20626747 | doi = 10.1111/j.1750-3639.2010.00394.x | s2cid = 24182017 | pmc = 8094635 }}</ref><ref name = "Porter">{{cite journal | vauthors = Ledford H | title = Cell therapy fights leukaemia | journal = Nature | year = 2011 | doi = 10.1038/news.2011.472 }}</ref><ref name="SloanKettering">{{cite web |vauthors=Coghlan A | date = 26 March 2013 | url = https://www.newscientist.com/article/mg21729104.100-gene-therapy-cures-leukaemia-in-eight-days.html | title = Gene therapy cures leukaemia in eight days | work = The New Scientist | access-date = 15 April 2013}}</ref>, koʻp sonli [[miyeloma]]<ref name="Adaptimmune">{{cite magazine | vauthors = Coghlan A | date = 11 December 2013 | url = https://www.newscientist.com/article/dn22613-soupedup-immune-cells-force-leukaemia-into-remission.html | title = Souped-up immune cells force leukaemia into remission | magazine = New Scientist | access-date = 15 April 2013 }}</ref>, [[gemofiliya]]<ref name="NewScientist1013">{{cite web | vauthors = Geddes L | title='Bubble kid' success puts gene therapy back on track | website=New Scientist | date=30 October 2013 | url=https://www.newscientist.com/article/mg22029413-200-bubble-kid-success-puts-gene-therapy-back-on-track/ | access-date=2 January 2022 }}</ref> va [[Parkinson kasalligi]]ni davolash kiradi<ref>{{cite journal | vauthors = LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Thomas K, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Van Meter L, Sapan CV, During MJ, Kaplitt MG, Feigin A | display-authors = 6 | title = AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial | journal = The Lancet. Neurology | volume = 10 | issue = 4 | pages = 309–319 | date = April 2011 | pmid = 21419704 | doi = 10.1016/S1474-4422(11)70039-4 | s2cid = 37154043 }}</ref>. 2013-yildan 2014-yil apreligacha boʻlgan davrda AQSH kompaniyalari ushbu sohaga 600 million dollardan ortiq sarmoya kiritdilar<ref name="Forbes">{{cite web | vauthors = Herper M | date = 26 March 2014 | url = https://www.forbes.com/sites/matthewherper/2014/03/26/once-seen-as-too-scary-editing-peoples-genes-with-viruses-makes-a-618-million-comeback/ | title = Gene Therapy's Big Comeback | work = Forbes | access-date = 28 April 2014 }}</ref>.

Birinchi tijoriy gen terapiyasi boʻlgan „[[Gendicine]]“ 2003-yilda [[Xitoy]]da saratonning ayrim turlarini davolash uchun maʼqullandi<ref name="Gend">{{cite journal | vauthors = Pearson S, Jia H, Kandachi K | title = China approves first gene therapy | journal = Nature Biotechnology | volume = 22 | issue = 1 | pages = 3–4 | date = January 2004 | pmid = 14704685 | doi = 10.1038/nbt0104-3 | pmc = 7097065 }}</ref>. 2011-yilda Rossiyada „Neovasculgen“ preparati oyoq-qoʻllarning kritik ishemiyasini oʻz ichiga olgan periferik arteriya kasalligini davolash boʻyicha oʻz sinfidagi birinchi gen terapiyasi dori vositasi sifatida roʻyxatga olindi<ref name="Neuvasculgen">{{cite news|title=Gene Therapy for PAD Approved|url=http://www.dddmag.com/news/2011/12/gene-therapy-pad-approved|access-date=5 August 2015|date=6 December 2011}}</ref>. 2012-yilda kam uchraydigan irsiy kasallik — lipoproteinlipaza yetishmovchiligini davolashga moʻljallangan „alipogene tiparvovec“ preparati Yevropa Komissiyasi tomonidan maʼqullanganidan soʻng, Yevropa Ittifoqi yoki AQSHda klinik foydalanish uchun ruxsat etilgan birinchi davolash vositasiga aylandi<ref name="Richards2012" /><ref name="Gallagher"/>.

Bakteriyalar, hujayralar va mayda hayvonlarni [[genetik muhandislik]] qilish boʻyicha dastlabki yutuqlardan soʻng, olimlar ushbu texnologiyani tibbiyotda qanday qoʻllash mumkinligi haqida oʻylay boshladilar. Bunda ikkita asosiy yondashuv koʻrib chiqildi: nuqsonli genlarni almashtirish yoki ularning faoliyatini toʻxtatish. Olimlar eʼtiborini kistik fibroz, gemofiliya, mushaklar distrofiyasi, talassemiya va oʻroqsimon hujayrali kamqonlik kabi bitta gen nuqsoni tufayli kelib chiqadigan kasalliklarga qaratdilar<ref>{{cite web | title=What is gene therapy? | website=Genetics Home Reference | date=28 March 2016 | url=https://medlineplus.gov/genetics/understanding/therapy/genetherapy/ | archive-url=https://web.archive.org/web/20160406021547/https://ghr.nlm.nih.gov/handbook/therapy/genetherapy | archive-date=6 April 2016 | url-status=live | access-date=2 January 2022}}</ref>. Masalan, „[[alipogene tiparvovec]]“ preparati aynan shunday kasalliklardan birini — lipoproteinlipaza fermenti nuqsoni tufayli yuzaga keladigan xastalikni davolaydi<ref name="Gallagher" />.

DNK organizmga yuborilishi, shikastlangan hujayralarga yetib borishi, hujayra ichiga kirishi va oqsilning ekspressiyasini taʼminlashi yoki uning faoliyatini toʻxtatishi lozim<ref>{{cite web | publisher = U.S. National Library of Medicine | work = Genomics Home Reference. | url = https://medlineplus.gov/genetics/understanding/therapy/procedures/ | title = How does gene therapy work? }}</ref>. Buning uchun koʻplab yetkazib berish usullari oʻrganilgan<ref name="pmid23015375">{{cite journal | vauthors = Pezzoli D, Chiesa R, De Nardo L, Candiani G | title = We still have a long way to go to effectively deliver genes! | journal = Journal of Applied Biomaterials & Functional Materials | volume = 10 | issue = 2 | pages = 82–91 | date = September 2012 | pmid = 23015375 | doi = 10.5301/JABFM.2012.9707 | s2cid = 6283455 }}</ref><ref name="pmid23435812">{{cite journal | vauthors = Vannucci L, Lai M, Chiuppesi F, Ceccherini-Nelli L, Pistello M | title = Viral vectors: a look back and ahead on gene transfer technology | journal = The New Microbiologica | volume = 36 | issue = 1 | pages = 1–22 | date = January 2013 | pmid = 23435812 }}</ref>. Dastlabki yondashuvda DNKni xromosomaga olib kirish uchun u maxsus muhandislik yoʻli bilan oʻzgartirilgan virus tarkibiga kiritilgan. Shuningdek, ayniqsa vaksinalar ishlab chiqish doirasida, „yalangʻoch“ DNK usullari ham tadqiq qilingan<ref name="pmid23111168">{{cite journal | vauthors = Gothelf A, Gehl J | title = What you always needed to know about electroporation based DNA vaccines | journal = Human Vaccines & Immunotherapeutics | volume = 8 | issue = 11 | pages = 1694–1702 | date = November 2012 | pmid = 23111168 | pmc = 3601144 | doi = 10.4161/hv.22062 }}</ref>.

Umuman olganda, harakatlar asosan zarur oqsilning ekspressiyasiga sabab boʻladigan genni kiritishga qaratilgan edi. Yaqin vaqtlar ichida nukleaza funksiyasi haqidagi tushunchalarning kengayishi ruxli barmoq nukleazalari va CRISPR kabi usullardan foydalangan holda DNKni toʻgʻridan-toʻgʻri tahrirlashga zamin yaratdi. Vektor genlarni xromosomalarga kiritadi. Shundan soʻng namoyon boʻlgan nukleazalar xromosomadagi genlarni bloklaydi va almashtiradi. 2014-yil holatiga koʻra, ushbu yondashuvlar bemorlardan hujayralarni ajratib olish, xromosomani tahrirlash va oʻzgartirilgan hujayralarni yana bemorlarga qaytarishni koʻzda tutadi<ref name="pmid20717154">{{cite journal | vauthors = Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD | title = Genome editing with engineered zinc finger nucleases | journal = Nature Reviews Genetics | volume = 11 | issue = 9 | pages = 636–646 | date = September 2010 | pmid = 20717154 | doi = 10.1038/nrg2842 | s2cid = 205484701 }}</ref>.

[[Gen tahrirlash]] irsiy kasalliklar, virusli kasalliklar va saratonni davolash uchun inson genomini oʻzgartirish imkonini beruvchi istiqbolli yondashuvdir<ref name="Bak 600–611">{{cite journal |vauthors=Bak RO, Gomez-Ospina N, Porteus MH |date=August 2018 |title=Gene Editing on Center Stage |journal=Trends in Genetics |volume=34 |issue=8 |pages=600–611 |doi=10.1016/j.tig.2018.05.004 |pmid=29908711 |s2cid=49269023}}</ref><ref>{{cite journal | vauthors = Stone D, Niyonzima N, Jerome KR | title = Genome editing and the next generation of antiviral therapy | journal = Human Genetics | volume = 135 | issue = 9 | pages = 1071–82 | date = September 2016 | pmid = 27272125 | pmc = 5002242 | doi = 10.1007/s00439-016-1686-2 }}</ref><ref>{{cite journal | vauthors = Cross D, Burmester JK | title = Gene therapy for cancer treatment: past, present and future | journal = Clinical Medicine & Research | volume = 4 | issue = 3 | pages = 218–27 | date = September 2006 | pmid = 16988102 | pmc = 1570487 | doi = 10.3121/cmr.4.3.218 }}</ref><ref>{{cite journal | vauthors = Maeder ML, Gersbach CA | title = Genome-editing Technologies for Gene and Cell Therapy | journal = Molecular Therapy | volume = 24 | issue = 3 | pages = 430–46 | date = March 2016 | pmid = 26755333 | pmc = 4786923 | doi = 10.1038/mt.2016.10 }}</ref>. 2020-yil holatiga koʻra, ushbu yondashuvlar klinik sinovlarda oʻrganilmoqda<ref>{{cite web|date=7 February 2019|title=Tests suggest scientists achieved 1st 'in body' gene editing|url=https://apnews.com/article/d728f86d70d94ce68dd4fedffe58d03f|access-date=17 November 2020|website=AP NEWS}}</ref><ref>{{cite journal|date=1 April 2020|title=First CRISPR therapy dosed|journal=Nature Biotechnology|volume=38|issue=4|page=382|doi=10.1038/s41587-020-0493-4|pmid=32265555|s2cid=215406440|issn=1546-1696|doi-access=free}}</ref>.

=== Genni tahrirlash ===
{{Main|CRISPR genini tahrirlash}}
Gen terapiyasining mohiyati genetik muammoni uning manbasida bartaraf etishdan iborat. Masalan, agar muayyan gendagi mutatsiya irsiy kasallikka (odatda retsessiv yoʻl bilan) olib keladigan funksional boʻlmagan oqsil hosil boʻlishiga sabab boʻlsa, gen terapiyasi zararli mutatsiyani oʻz ichiga olmagan ushbu gen nusxasini hujayraga yetkazib berish va shu orqali funksional oqsil hosil boʻlishini taʼminlash uchun qoʻllanishi mumkin. Ushbu strategiya genni almashtirish terapiyasi deb ataladi va u irsiy retinal kasalliklarni davolashda qoʻllanishi mumkin<ref name="Maguire 2008" /><ref name="pmid24439297">{{cite journal | vauthors = MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, Clark KR, During MJ, Cremers FP, Black GC, Lotery AJ, Downes SM, Webster AR, Seabra MC | title = Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial | journal = Lancet | volume = 383 | issue = 9923 | pages = 1129–1137 | date = March 2014 | pmid = 24439297 | pmc = 4171740 | doi = 10.1016/S0140-6736(13)62117-0 }}</ref>.

Genni almashtirish terapiyasi konsepsiyasi asosan retsessiv kasalliklar uchun mos boʻlsa-da, dominant irsiylanish turiga ega kasalliklarni ham davolash imkonini beradigan yangi strategiyalar taklif etilgan.
* [[CRISPR gen tahrirlash]] texnologiyasining joriy etilishi gen terapiyasini qoʻllash va undan foydalanish uchun yangi imkoniyatlarni ochdi<ref name="Bak 600–611" />. Chunki u genni shunchaki almashtirish oʻrniga, muayyan genetik nuqsonni tuzatish imkonini beradi. Kelajakda yashirin [[OIV|inson immunitet tanqisligi virusi (OIV)]] rezervuarlarini yoʻq qilish hamda oʻroqsimon hujayrali kasallikni keltirib chiqaruvchi mutatsiyani tuzatish kabi tibbiy muammolarni davolash usuli sifatida qoʻllanishi mumkin<ref>{{cite journal |display-authors=6 |vauthors=Dever DP, Bak RO, Reinisch A, Camarena J, Washington G, Nicolas CE, Pavel-Dinu M, Saxena N, Wilkens AB, Mantri S, Uchida N, Hendel A, Narla A, Majeti R, Weinberg KI, Porteus MH |date=November 2016 |title=CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells |journal=Nature |volume=539 |issue=7629 |pages=384–389 |bibcode=2016Natur.539..384D |doi=10.1038/nature20134 |pmc=5898607 |pmid=27820943}}</ref><ref>{{cite journal |vauthors=Gupta RM, Musunuru K |date=October 2014 |title=Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9 |journal=The Journal of Clinical Investigation |volume=124 |issue=10 |pages=4154–61 |doi=10.1172/JCI72992 |pmc=4191047 |pmid=25271723 |bibcode=2014JCliI.124.4154G }}</ref><ref>{{cite journal |vauthors=Sanches-da-Silva GN, Medeiros LF, Lima FM |date=21 August 2019 |title=The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy |journal=International Journal of Genomics |volume=2019 |article-number=8458263 |doi=10.1155/2019/8458263 |pmc=6721108 |pmid=31531340 |doi-access=free}}</ref>.
* Protez gen terapiyasi organizm hujayralariga odatda fiziologik jihatdan bajarmaydigan funksiyalarni bajarish imkonini berishni maqsad qiladi. Bunga misol sifatida koʻrishni tiklashga qaratilgan gen terapiyasini keltirish mumkin<ref>Patent: US7824869B2</ref><ref>{{cite journal |vauthors=Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, Pan ZH |date=April 2006 |title=Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration |journal=Neuron |volume=50 |issue=1 |pages=23–33 |doi=10.1016/j.neuron.2006.02.026 |pmc=1459045 |pmid=16600853 |doi-access=free}}</ref>. U terminal bosqichdagi retinal kasalliklarga chalingan bemorlarda koʻrish qobiliyatini tiklashni maqsad qiladi. Terminal bosqichdagi retinal kasalliklarda toʻr pardaning yorugʻlikni qabul qiluvchi asosiy hujayralari boʻlgan fotoretseptorlar qaytarib boʻlmaydigan darajada yoʻqoladi. Protez gen terapiyasi yordamida yorugʻlikka sezgir oqsillar toʻr pardaning saqlanib qolgan hujayralariga yetkazib beriladi. Natijada bu hujayralar yorugʻlikka sezgir boʻlib, koʻrish axborotini miyaga uzata oladi.
In vivo sharoitida [[CRISPR]] asosidagi gen tahrirlash tizimlari saratonni davolash maqsadida sichqonlarda oʻtkazilgan tadqiqotlarda qoʻllanilgan va oʻsmalarni kamaytirishda samarali boʻlgan<ref name=":8">{{Cite journal |last1=Song |first1=Xiangrong |last2=Liu |first2=Chao |last3=Wang |first3=Ning |last4=Huang |first4=Hai |last5=He |first5=Siyan |last6=Gong |first6=Changyang |last7=Wei |first7=Yuquan |date=1 January 2021 |title=Delivery of CRISPR/Cas systems for cancer gene therapy and immunotherapy |url=https://www.sciencedirect.com/science/article/pii/S0169409X20300302 |journal=Advanced Drug Delivery Reviews |series=Delivery of Biomacromolecules for Therapeutic Genome Editing |volume=168 |pages=158–180 |doi=10.1016/j.addr.2020.04.010 |pmid=32360576 |s2cid=218493473 |issn=0169-409X|url-access=subscription }}</ref>. In vitro sharoitida esa CRISPR tizimi [[HPV]] bilan bogʻliq saraton oʻsmalarini davolashda qoʻllanilgan. CRISPR tizimi uchun genomni hujayralarga kiritishda [[Adeno-associated virus]] va [[Lentivirus]] asosidagi vektorlardan foydalanilgan<ref name=":8" />.

== Vektorlar ==
{{Main|Gen terapiyasida vektorlar}}
DNKni hujayralarga yetkazib berish [[Gen terapiyasidagi vektorlar|bir necha usullar]] orqali amalga oshirilishi mumkin. Ularning ikkita asosiy toifasi [[rekombinant virus]]lar (baʼzan biologik nanohissachalar yoki virusli vektorlar deb ataladi) hamda yalangʻoch DNK yoki DNK komplekslari (virussiz usullar) hisoblanadi<ref>{{cite journal | vauthors = Nayerossadat N, Maedeh T, Ali PA | title = Viral and nonviral delivery systems for gene delivery | journal = Advanced Biomedical Research | volume = 1 | issue = 1 | page = 27 | date = 2012 | pmid = 23210086 | pmc = 3507026 | doi = 10.4103/2277-9175.98152 | doi-access = free }}</ref>.

=== Viruslar ===
{{Main|Virusli tashuvchi}}
[[File:Gene therapy.jpg|thumb|[[Adenovirus]] vektori yordamida amalga oshiriladigan gen terapiyasi. Ayrim hollarda adenovirus yangi genni hujayraga kiritadi. Agar davolash muvaffaqiyatli boʻlsa, yangi gen kasallikni davolash uchun funksional [[oqsil]] hosil qiladi.]]
[[Virus]]lar koʻpayish uchun oʻz genetik materialini xoʻjayin hujayraga kiritadi va xoʻjayin hujayraning hujayraviy mexanizmlarini virus oqsillarini ishlab chiqarish uchun andoza sifatida undan foydalanishga majbur qiladi<ref name=":4">{{Cite book | vauthors = Nóbrega C, Mendonça L, Matos CA |title=A handbook of gene and cell therapy |date=2020 |publisher=Springer |isbn=978-3-030-41333-0 |location=Cham |oclc=1163431307}}</ref>. [[Retrovirus]]lar esa bundan ham bir qadam oldinga borib, oʻz genetik materialining xoʻjayin hujayra yadrosi genomiga koʻchirilishini taʼminlaydi. Olimlar virus genetik materialining bir qismini davolovchi DNK yoki RNK bilan almashtirish orqali ushbu xususiyatdan foydalanadilar<ref name=":4" /><ref name=":2">{{cite journal |vauthors=Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR |date=May 2018 |title=Gene therapy clinical trials worldwide to 2017: An update |journal=The Journal of Gene Medicine |volume=20 |issue=5 |article-number=e3015 |doi=10.1002/jgm.3015 |pmid=29575374 |s2cid=4966300|doi-access=free }}</ref>. Viruslardagi genetik material (DNK yoki RNK) singari, davolovchi genetik material ham integratsiyalanmaydigan vektorlarda boʻlgani kabi tabiiy ravishda parchalanib ketadigan vaqtinchalik andoza sifatida yoki xoʻjayin hujayra yadrosiga kirib, zararlangan hujayralarda xoʻjayinning yadro DNKsi tarkibining doimiy qismiga aylanishi uchun loyihalanishi mumkin<ref name=":4" />.

Insonlarda gen terapiyasida [[lentivirus]], [[adenovirus]], [[herpes simplex virus|gerpes simpleks virusi]], [[vaccinia virus|vaksiniya virusi]] va [[adeno-associated virus]] kabi bir qator viruslardan foydalanilgan<ref name="JGenMed Database" />.

[[Adenoviridae|Adenovirus virusli vektorlari]] (Ad) xoʻjayin hujayrasi DNKsiga integratsiyalanmaydigan genetik material yordamida hujayraning genetik ifodalanishini vaqtincha oʻzgartiradi<ref name=":3">{{cite journal | vauthors = Bulcha JT, Wang Y, Ma H, Tai PW, Gao G | title = Viral vector platforms within the gene therapy landscape | journal = Signal Transduction and Targeted Therapy | volume = 6 | issue = 1 | article-number = 53 | date = February 2021 | pmid = 33558455 | pmc = 7868676 | doi = 10.1038/s41392-021-00487-6 }}</ref>. 2017-yil holatiga koʻra, bunday vektorlar gen terapiyasi boʻyicha klinik sinovlarning 20% ida qoʻllanilgan<ref name=":2" />. Adenovirus vektorlari asosan saraton kasalliklarini davolashda hamda [[Ebola vaksinasi]], [[OIV]] va [[SARS-CoV-2]] uchun klinik sinovlarda qoʻllanilgan vaksinalar, shuningdek, [[saraton vaksinasi]] kabi yangi genetik vaksinalarda qoʻllaniladi<ref name=":3" />.

[[Gen terapiyasida lentivirusli vektor|Lentivirusli vektorlar]] [[lentivirus]]ga mansub [[retrovirus]] asosida yaratilgan boʻlib, hujayra yadrosidagi [[genom]]ni oʻzgartirib, genning doimiy ifodalanishini taʼminlashi mumkin<ref name=":4" />, biroq vektorlar integratsiyalanishning oldini oladigan tarzda ham modifikatsiya qilinishi mumkin<ref name=":2" />. 2018-yilgacha retroviruslar gen terapiyasi boʻyicha klinik sinovlarning 18% ida qoʻllanilgan. [[Atidarsagene autotemcel|Libmeldy]] [[metaxromatik leykodistrofiya]]ni davolash uchun ex vivo ildiz hujayra terapiyasi boʻlib, unda lentivirusli vektordan foydalaniladi va u 2020-yilda Yevropa dori vositalari agentligi tomonidan tasdiqlangan<ref>{{Cite journal |last1=Jensen |first1=Thomas Leth |last2=Gøtzsche |first2=Casper René |last3=Woldbye |first3=David P. D. |date=2021 |title=Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord |journal=Frontiers in Molecular Neuroscience |volume=14 |article-number=695937 |doi=10.3389/fnmol.2021.695937 |pmid=34690692 |pmc=8527017 |issn=1662-5099 |doi-access=free }}</ref>.

[[Adeno-associated virus]] (AAV) hujayra boshqa virus, yaʼni yordamchi virus bilan zararlanmagan boʻlsa, hujayralar oʻrtasida tarqala olmaydigan virusdir. [[Adenovirus]] va gerpes viruslari AAV uchun yordamchi virus vazifasini bajaradi<ref>{{cite journal | vauthors = Manini A, Abati E, Nuredini A, Corti S, Comi GP | title = Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Duchenne Muscular Dystrophy: The Issue of Transgene Persistence | journal = Frontiers in Neurology | volume = 12 | article-number = 814174 | date = 2022 | pmid = 35095747 | pmc = 8797140 | doi = 10.3389/fneur.2021.814174 | doi-access = free }}</ref>. AAV asosan [[concatemer|konkatemer]]lar hosil qilib, ular koʻpincha [[episome|episoma]]lar shaklida tashkil topgani sababli hujayra yadrosi genomidan tashqarida uzoq vaqt saqlanib qoladi. AAV vektorlarining genetik materiali xoʻjayin hujayrasi yadro genomiga past chastotada integratsiyalanadi va bu jarayon, ehtimol, xoʻjayin hujayrasining DNKni oʻzgartiruvchi fermentlari vositasida amalga oshadi<ref name=":7">{{cite journal | vauthors = Sabatino DE, Bushman FD, Chandler RJ, Crystal RG, Davidson BL, Dolmetsch R, Eggan KC, Gao G, Gil-Farina I, Kay MA, McCarty DM, Montini E, Ndu A, Yuan J | display-authors = 6 | title = Evaluating the state of the science for adeno-associated virus integration: An integrated perspective | language = English | journal = Molecular Therapy | volume = 30 | issue = 8 | pages = 2646–2663 | date = August 2022 | pmid = 35690906 | pmc = 9372310 | doi = 10.1016/j.ymthe.2022.06.004 }}</ref>. Hayvonlar modellaridagi tadqiqotlar AAV genetik materialining xoʻjayin hujayrasi yadro genomiga integratsiyalanishi [[gepatotsellyulyar karsinoma]], yaʼni [[jigar saratoni]]ning bir shaklini keltirib chiqarishi mumkinligini koʻrsatadi<ref name=":7" />. Inson kasalliklarida AAV gen terapiyasini qoʻllashning istiqbolli yoʻnalishlaridan biri sifatida yoshga bogʻliq makula degeneratsiyasini davolash uchun bir nechta AAV asosidagi tadqiqot preparatlari intravitreal va subretinal usullar orqali oʻrganilgan<ref>{{cite journal |title=Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study |journal=Lancet |date=2024 |pmid=38554726 |last1=Campochiaro |first1=P. A. |last2=Avery |first2=R. |last3=Brown |first3=D. M. |last4=Heier |first4=J. S. |last5=Ho |first5=A. C. |last6=Huddleston |first6=S. M. |last7=Jaffe |first7=G. J. |last8=Khanani |first8=A. M. |last9=Pakola |first9=S. |last10=Pieramici |first10=D. J. |last11=Wykoff |first11=C. C. |last12=Van Everen |first12=S. |volume=403 |issue=10436 |pages=1563–1573 |doi=10.1016/S0140-6736(24)00310-6 }}</ref><ref>{{cite journal |title=Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective, two-year, multicentre phase 1 study |journal=eClinicalMedicine |date=2024 |pmid=38152412 |last1=Khanani |first1=A. M. |last2=Boyer |first2=D. S. |last3=Wykoff |first3=C. C. |last4=Regillo |first4=C. D. |last5=Busbee |first5=B. G. |last6=Pieramici |first6=D. |last7=Danzig |first7=C. J. |last8=Joondeph |first8=B. C. |last9=Major Jr |first9=J. C. |last10=Turpcu |first10=A. |last11=Kiss |first11=S. |volume=67 |article-number=102394 |doi=10.1016/j.eclinm.2023.102394 |pmc=10751837 }}</ref>.

== Virusli boʻlmaganlar ==
Gen terapiyasi uchun [[virussiz vektor]]lar virusli usullarga nisbatan ayrim afzalliklarga ega, jumladan, yirik miqyosda ishlab chiqarish imkoniyati va xoʻjayinning past [[immunogenlik]] darajasi<ref>{{cite journal | vauthors = Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG | title = Non-viral vectors for gene-based therapy | journal = Nature Reviews. Genetics | volume = 15 | issue = 8 | pages = 541–555 | date = August 2014 | pmid = 25022906 | doi = 10.1038/nrg3763 | s2cid = 15273455 }}</ref>. Biroq dastlab virussiz usullar [[transfeksiya]] va [[gen ekspressiyasi]]ning past darajasini taʼminlagan, natijada ularning davolash samaradorligi ham past boʻlgan. Hujayraga xos harakatlanish va hujayra ichidagi tashishni boshqarish texnologiyalarining rivojlanishi bilan ushbu muammolarni bartaraf etish imkoniyatlari paydo boʻlmoqda.

[[Gen terapiyasidagi vektorlar#Virussiz usullar|Virussiz gen terapiyasi usullari]] qatoriga yalangʻoch DNKni yuborish, [[elektroporatsiya]], [[gen quroli]], [[sonoporatsiya]], [[magnetofeksiya]], [[oligonukleotid]]lardan, lipoplekslardan, dendrimerlardan va noorganik nanohissachalardan foydalanish kiradi. Ushbu davolash usullari bevosita yoki [[To‘qima muhandisligi|skafold bilan boyitish]] orqali qoʻllanilishi mumkin<ref>{{Cite journal |last1=Krasilnikova |first1=O. |last2=Yakimova |first2=A. |last3=Ivanov |first3=S. |last4=Atiakshin |first4=D. |last5=Kostin |first5=A.A. |last6=Sosin |first6=D. |last7=Shegay |first7=P. |last8=Kaprin |first8=A.D. |last9=Klabukov |first9=I. |date=2023 |title=Gene-Activated Materials in Regenerative Dentistry: Narrative Review of Technology and Study Results |journal=International Journal of Molecular Sciences |volume=24 |issue=22 |article-number=16250 |doi=10.3390/ijms242216250 |doi-access=free |issn=1422-0067 |pmc=10671237 |pmid=38003439}}</ref><ref>{{Cite journal |last1=Foldvari |first1=M. |last2=Chen |first2=D.W. |last3=Nafissi |first3=N. |last4=Calderon |first4=D. |last5=Narsineni |first5=L. |last6=Rafiee |first6=A. |date=2016 |title=Non-viral gene therapy: Gains and challenges of non-invasive administration methods |journal=Journal of Controlled Release|volume=240 |pages=165–190 |doi=10.1016/j.jconrel.2015.12.012 |issn=1873-4995 |pmid=26686079}}</ref>.

[[Ligandal]] kabi kompaniyalar tomonidan ishlab chiqilgan zamonaviy yondashuvlar RNK, DNK va [[CRISPR]] kabi genlarni tahrirlash vositalarini oʻz ichiga olgan turli gen terapiyasi usullari uchun hujayraga xos nishonlash texnologiyalarini yaratish imkonini bermoqda. [[Arbutus Biopharma]] va [[Arcturus Therapeutics]] kabi boshqa kompaniyalar esa asosan jigarga yoʻnaltirilgan tropizmni namoyon etuvchi, viruslardan foydalanmaydigan va muayyan hujayralarni nishonga olmaydigan yondashuvlarni taklif etmoqda. Soʻnggi yillarda [[Sixfold Bio]], [[Nanite]], [[GenEdit]] va [[Spotlight Therapeutics]] kabi startaplar ham virussiz gen yetkazib berish muammosini hal etishga kirishdi. Virussiz usullar davolashni takroran qoʻllash hamda genetik yukni yanada moslashuvchan tarzda loyihalash imkonini beradi va kelajakda ular virusga asoslangan yetkazib berish tizimlari oʻrnini egallashi ehtimoli yuqori.

[[Editas Medicine]], [[Intellia Therapeutics]], [[CRISPR Therapeutics]], [[Casebia]], [[Cellectis]], [[Precision Biosciences]], [[bluebird bio]], [[Excision BioTherapeutics]] va [[Sangamo]] kabi kompaniyalar virussiz genlarni tahrirlash texnologiyalarini ishlab chiqqan. Biroq ular yoʻnaltirilgan [[nukleaza]]lar yordamida genom kesilgandan soʻng genni kiritish materialini yetkazib berishda koʻpincha hanuz viruslardan foydalanadi. Ushbu kompaniyalar asosan genlarni tahrirlashga eʼtibor qaratgan boʻlsa-da, genlarni yetkazib berish bilan bogʻliq muhim muammolarga hali ham duch kelmoqda.

[[BioNTech]], [[Moderna Therapeutics]] va [[CureVac]] [[mRNK]]ni yetkazib berishga ixtisoslashgan boʻlib, bu esa tabiatan virussiz yetkazib berish usullarini talab qiladi.

[[Alnylam]], [[Dicerna Pharmaceuticals]] va [[Ionis Pharmaceuticals]] gen ekspressiyasini bostirish uchun [[siRNK]] (antisens oligonukleotidlar)ni yetkazib berishga ixtisoslashgan boʻlib, bu ham virussiz yetkazib berish tizimlarini talab etadi.

Akademik tadqiqotlarda bir qator laboratoriyalar [[Polyethylene glycol|PEG]] bilan modifikatsiya qilingan zarrachalarni yetkazib berish ustida ishlamoqda. Bunday zarrachalar zardob [[oqsil koronasi]]ni hosil qiladi va ''in vivo'' sharoitida hujayralarga asosan [[LDL retseptori]] vositasidagi qabul qilinishni namoyon etadi<ref>{{cite journal | vauthors = Bertrand N, Grenier P, Mahmoudi M, Lima EM, Appel EA, Dormont F, Lim JM, Karnik R, Langer R, Farokhzad OC | display-authors = 6 | title = Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics | journal = Nature Communications | volume = 8 | issue = 1 | article-number = 777 | date = October 2017 | pmid = 28974673 | pmc = 5626760 | doi = 10.1038/s41467-017-00600-w | bibcode = 2017NatCo...8..777B }}</ref>.

== Manbalar ==
{{manbalar|2}}

== Qoʻshimcha oʻqish uchun ==
{{refbegin|30em}}
* {{cite journal | title=Gene Therapy: An Overview of Approved and Pipeline Technologies | journal=CADTH | url=https://cadth.ca/sites/default/files/pdf/eh0068_gene_therapy.pdf | archive-url=https://web.archive.org/web/20181019222316/https://www.cadth.ca/sites/default/files/pdf/eh0068_gene_therapy.pdf | archive-date=19 October 2018 | url-status=live | issue=171 | date=March 2018 | access-date=2026-07-16 | archivedate=2018-10-19 | archiveurl=https://web.archive.org/web/20181019222316/https://www.cadth.ca/sites/default/files/pdf/eh0068_gene_therapy.pdf }}
* {{cite journal | vauthors = Baum C, Düllmann J, Li Z, Fehse B, Meyer J, Williams DA, von Kalle C | title = Side effects of retroviral gene transfer into hematopoietic stem cells | url = https://archive.org/details/sim_blood_2003-03-15_101_6/page/2099 | journal = Blood | volume = 101 | issue = 6 | pages = 2099–2114 | date = March 2003 | pmid = 12511419 | doi = 10.1182/blood-2002-07-2314 | s2cid = 8489829 }}
* {{cite journal | vauthors = Daley J | date = January 2020 | title = Gene Therapy Arrives: After false starts, drugs that manipulate the code of life are finally changing lives | journal = Scientific American | volume = 322 | issue = 1 | pages = None | doi = 10.1038/scientificamerican012020-2SglZYN24KkpjWDUVuCdME | pmid = 39014835 | url = https://www.scientificamerican.com/article/gene-therapy-arrives/ | url-access = subscription }}
* {{cite journal | vauthors = Gardlík R, Pálffy R, Hodosy J, Lukács J, Turna J, Celec P | title = Vectors and delivery systems in gene therapy | journal = Medical Science Monitor | volume = 11 | issue = 4 | pages = RA110–121 | date = April 2005 | pmid = 15795707 }}
* {{cite journal | vauthors = Horn PA, Morris JC, Neff T, Kiem HP | title = Stem cell gene transfer – efficacy and safety in large animal studies | journal = Molecular Therapy | volume = 10 | issue = 3 | pages = 417–431 | date = September 2004 | pmid = 15336643 | doi = 10.1016/j.ymthe.2004.05.017 | doi-access = free }}
* {{cite journal | vauthors = Parambi DG, Alharbi KS, Kumar R, Harilal S, Batiha GE, Cruz-Martins N, Magdy O, Musa A, Panda DS, Mathew B | title = Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases | journal = Molecular Neurobiology | date = October 2021 | volume = 59 | issue = 1 | pages = 191–233 | pmid = 34655056 | pmc = 8518903 | doi = 10.1007/s12035-021-02555-y }}
* {{cite journal | vauthors = Salmons B, Günzburg WH | title = Targeting of retroviral vectors for gene therapy | journal = Human Gene Therapy | volume = 4 | issue = 2 | pages = 129–141 | date = April 1993 | pmid = 8494923 | doi = 10.1089/hum.1993.4.2-129 }}
* {{cite web | last = Staff|date= 18 November 2005 | url = http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml | title = Gene Therapy| format = FAQ| work = Human Genome Project Information | publisher = [[Oak Ridge National Laboratory]] | access-date = 28 May 2006|archive-url=https://web.archive.org/web/20060427174645/http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml|archive-date=27 April 2006}}
* {{cite web | vauthors = Tinkov S, Bekeredjian R, Winter G, Coester C | title = Polyplex-conjugated microbubbles for enhanced ultrasound targeted gene therapy | publisher = 2008 AAPS Annual Meeting and Exposition | date = 20 November 2000 | location = [[Georgia World Congress Center]], Atlanta, GA | url = http://www.aapsj.org/abstracts/AM_2008/AAPS2008-000838.PDF | access-date = 26 January 2009 | archive-url = https://web.archive.org/web/20120707180351/http://www.aapsj.org/abstracts/AM_2008/AAPS2008-000838.PDF | archive-date = 7 July 2012 }}
* {{cite journal | vauthors = Wang H, Shayakhmetov DM, Leege T, Harkey M, Li Q, Papayannopoulou T, Stamatoyannopolous G, Lieber A | title = A capsid-modified helper-dependent adenovirus vector containing the beta-globin locus control region displays a nonrandom integration pattern and allows stable, erythroid-specific gene expression | journal = Journal of Virology | volume = 79 | issue = 17 | pages = 10999–11013 | date = September 2005 | pmid = 16103151 | pmc = 1193620 | doi = 10.1128/JVI.79.17.10999-11013.2005 }}
{{refend}}

[[Turkum:Biotexnologiya]]
[[Turkum:Gen terapiyasi]]
[[Turkum:Genetik muhandislik]]