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Current Status of the Clinical Development of Gene Therapy
Biomed Sci Letters 2018;24:157-167
Published online September 30, 2018;  https://doi.org/10.15616/BSL.2018.24.3.157
© 2018 The Korean Society For Biomedical Laboratory Sciences.

Sun-Il Kwon†,*

Department of Biomedical Laboratory Science, Deagu Health Science University, Daegu 41453, Korea
Correspondence to: Sun-Il Kwon. Department of Biomedical Laboratory Science, Deagu Health Science University, Youngsong-ro 15 (Taejeon-dong), Buk-ku, Daegu 41453, Korea. Tel: +82-53-320-1870, Fax: +82-53-320-1450, e-mail: psikwon@dhc.ac.kr
Received July 10, 2018; Revised September 3, 2018; Accepted September 4, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract

The concept of gene therapy is to treat a disease by transferring therapeutic nucleic acids to a patient’s cells. It took several decades from the basic theoretical proposal of gene therapy to the current promising treatment option for some important human diseases. The encountered adverse effects in the early clinical studies boosted the development of sophisticated vectors and elaborate clinical designs. The gene therapy is now considered to have the potential to cure many diseases that are incurable with conventional medications. By the end of 2017, about 2,600 clinical trials of gene therapy have been performed or are ongoing for a variety of diseases such as cancers, monogenic diseases, cardiovascular diseases and neurological diseases etc. Here, we present a brief introduction of technical achievement in relation to gene therapy development, and a review of the current status of global gene therapy clinical development.

Keywords : Gene therapy, Cancer, Clinical study, Vector, Target diseases, Guidelines
꽌濡

쑀쟾옄移섎즺뒗 吏덈퀝쓣 移섎즺븯湲 쐞븯뿬 빑궛쓣 솚옄쓽 꽭룷 궡濡 닾뿬븯뒗 移섎즺諛⑸쾿씠떎. 醫낅옒쓽 移섎즺諛⑸쾿 吏덈퀝씠 諛쒖깮븳 썑 臾쇰━쟻쑝濡 썝씤쓣 젣嫄고븯嫄곕굹 솕빀臾쇱쓣 닾뿬븯뿬 吏덈퀝쓽 썝씤 臾쇱쭏쓣 뼲젣븯뒗 諛⑸쾿씠 二쇨 릺뿀뒗뜲 諛섑븯뿬, 쑀쟾옄移섎즺뒗 솚옄쓽 쑀쟾옄 옄泥대 蹂삎떆耳쒖꽌 吏덈퀝쓽 썝씤쓣 젣嫄고븯嫄곕굹 鍮꾩젙긽 쑀쟾옄媛 젣 湲곕뒫쓣 븯룄濡 룙뒗 移섎즺諛⑸쾿씠떎. 利 쑀쟾옄濡 씤븯뿬 諛쒖깮맂 吏덈퀝쓽 寃쎌슦뿉 쑀쟾쟻씤 썝씤 洹 옄泥대 젣뼱븯뒗 諛⑸쾿씠떎.

쑀쟾옄移섎즺뒗 쁽옱濡쒖꽌 留덈븙븳 移섎즺諛⑸쾿씠 뾾뒗 닔留롮 궃移섏꽦吏덊솚쓣 쑀쟾옄 닔以뿉꽌 洹쇰낯쟻쑝濡 移섎즺븷 닔 엳뒗 李⑥꽭 移섎즺湲곗닠씠떎. 쑀쟾옄移섎즺踰뺤쓽 긽씠 릺怨 엳뒗 蹂묒 嫄곗쓽 紐⑤뱺 醫낅쪟쓽 븫, 삁슦蹂 벑쓽 쑀쟾꽦吏덊솚, AIDS 벑쓽 媛먯뿼꽦吏덊솚, 떖삁愿怨꾩쭏솚 벑쑝濡 떎뼇븯떎. 긽떦븳 遺媛媛移섎 李쎌텧븷 닔 엳뒗 泥⑤떒湲곗닠濡쒖꽌 쟻슜踰붿쐞媛 꼻뼱꽌 꽭怨꾩쟻쑝濡 鍮꾩긽븳 愿떖쓣 걣怨 엳뒗 遺꾩빞씠떎.

쑀쟾옄移섎즺뒗 21꽭湲곕 넻븯뿬 뿴由 遺꾩옄쓽븰떆뿉 꽭룷移섎즺踰뺢낵 븿猿 以묒떖쟻씠怨 沅곴레쟻씤 移섎즺諛⑸쾿쑝濡 옄由щ 옟쓣 寃껋쑝濡 쟾留앸맂떎. 吏궃 30뿬뀈 媛 끂젰쓽 寃곗떎濡 理쒓렐 닔뀈 룞븞 뿬윭 媛쒖쓽 쑀留앺븳 쑀쟾옄移섎즺젣媛 듅씤릺뼱 異쒖떆릺湲 떆옉뻽떎. 쁽옱 꽭怨 룄泥섏뿉꽌 以묒슂븳 쑀쟾옄移섎즺젣 뿰援ш 吏꾪뻾릺怨 엳쑝硫, 議곕쭔媛 쑀쟾옄移섎즺 떆媛 蹂멸꺽쟻쑝濡 媛쒗솕맆 寃껋쑝濡 쟾留앸맂떎. 蹂멸퀬뿉꽌뒗 쑀쟾옄移섎즺젣 뿰援ъ쓽 쁽솴怨 룞뼢쓣 怨좎같빐蹂닿퀬옄 븳떎.

쑀쟾옄移섎즺젣 媛쒕컻쓽 湲곗닠쟻 湲곕컲

쑀쟾옄移섎즺젣쓽 젙쓽

쑀쟾옄移섎즺뒗 鍮꾩젙긽 룎뿰蹂씠 쑀쟾옄瑜 젙긽 쑀쟾옄濡 泥댁떆耳쒖꽌 쑀쟾쟻 寃고븿쓣 移섎즺븯뒗 諛⑸쾿씠떎. 꼻寃 蹂대㈃ 솚옄쓽 쑀쟾泥 援ъ꽦뿉 蹂솕瑜 二쇱뼱 쑀쟾쟻 寃고븿쓣 援먯젙븯뒗 紐⑤뱺 移섎즺뻾쐞瑜 쑀쟾옄移섎즺濡 媛꾩<븷 닔 엳떎.

쑀쟾옄濡 移섎즺븯뒗 쑀쟾옄移섎즺젣쓽 젙쓽뒗 媛곴뎅쓽 洹쒖젣 湲곌留덈떎 媛곴린 떎瑜 궗젙뿉 뵲씪꽌 젙빐졇꽌 꽌濡 議곌툑뵫 떎瑜대떎. 슦由щ굹씪뒗 ’깮臾쇳븰쟻젣젣 벑쓽 뭹紐⑺뿀媛 떖궗洹쒖젙’ 젣2議곗뿉 뵲씪 “吏덈퀝移섎즺 벑쓣 紐⑹쟻쑝濡 씤泥댁뿉 닾엯릺뒗 쑀쟾臾쇱쭏 삉뒗 쑀쟾臾쇱쭏쓣 룷븿븯怨 엳뒗 쓽빟뭹”쑝濡 洹쒖젙븯怨 엳떎. 誘멸뎅 FDA쓽 寃쎌슦뿉뒗 Guidance for Human Somatic Cell Therapy and Gene Therapy (Mar, 1998)뿉꽌 쑀쟾옄移섎즺瑜 젙쓽븯怨 엳떎. 씠 Guidance쓽 ’Definition of somatic cell therapy and gene therapy’ 遺遺꾩뿉꽌 “쑀쟾옄移섎즺뒗 궡븘엳뒗 꽭룷뿉 쑀쟾臾쇱쭏쓣 룄엯븯뒗뜲 湲곗큹븳 쓽猷뚭린닠濡쒖꽌, 꽭룷瑜 泥댁쇅뿉꽌 議곗옉븯뿬 씤泥대줈 닾뿬븯嫄곕굹 쑀쟾옄瑜 깮泥 궡濡 吏곸젒닾뿬븯뿬 쑀쟾옄瑜 移섎즺븳떎. 泥댁쇅뿉꽌 꽭룷쓽 쑀쟾옄瑜 議곗옉븯뿬 솚옄뿉寃 닾뿬븯뒗 寃쎌슦 泥댁꽭룷移섎즺쓽 븳 삎깭媛 맂떎. 쑀쟾옄議곗옉 移섎즺, 삁諛 삉뒗 듅젙 꽭룷쓽 궗썑 異붿쟻쓣 쐞븯뿬 닔뻾맂떎”.씪怨 젙쓽릺뼱 엳떎(Ser et al., 2015).

쑀읇 쓽빟뭹媛먮룆援(European Medicines Agency, EMA)뿉꽌뒗 쑀쟾옄移섎즺젣瑜 “(a) 쑀쟾옄 꽌뿴쓣 議곗젅, 닔젙, 泥, 異붽, 삉뒗 냼떎떆궎湲 쐞븯뿬 씤泥댁뿉 닾뿬릺뒗 옱議고빀 빑궛쓣 솢꽦꽦遺꾩쑝濡 븿쑀븯뒗 寃껋쑝濡, (b) 쑀쟾옄移섎즺젣쓽 移섎즺, 삁諛 삉뒗 吏꾨떒슚怨쇰뒗 옱議고빀 빑궛 꽌뿴뿉 쓽븯嫄곕굹 씠 꽌뿴쓽 쑀쟾쟻 諛쒗쁽 궛臾쇱뿉 쓽븳 寃껋씠떎”씪怨 젙쓽븳떎(Part IV of Annex I to Directive 2001/83/EC) (Seo et al., 2015).

쑀쟾옄移섎즺젣 媛쒕컻쓽 젒洹 諛⑹떇

쑀쟾옄移섎즺뒗 吏덊솚쓽 洹쇰낯썝씤쓣 遺꾩옄닔以뿉꽌 洹쒕챸븯뿬 移섎즺븯誘濡 利앹슂踰뺤씠 븘땶 洹쇱썝쟻씤 移섎즺媛 媛뒫빐吏꾨떎. 떎瑜 移섎즺젣媛 몴쟻솕븯湲 옒뱺 몴쟻룄 吏덈퀝쓽 湲곗쟾쓣 븣怨, 썝씤 쑀쟾옄瑜 젙솗엳 뙆븙븯硫 몴쟻솕媛 媛뒫븯湲 븣臾몄뿉 궃移섎퀝쓽 移섎즺뿉 理쒖쟻씠씪 븷 닔 엳떎.

쑀쟾옄移섎즺뿉꽌뒗 몢 媛吏 젒洹 諛⑹떇씠 엳뒗뜲 寃고븿 쑀쟾옄瑜 젙긽 쑀쟾옄濡 泥댄븯嫄곕굹, 寃고븿 쑀쟾옄瑜 臾대젰솕(disruption)떆궎뒗 諛⑸쾿씠떎. 移섎즺슜 DNA뒗 닾뿬맂 썑 紐⑺몴븯뒗 꽭룷뿉 룄떖븯뿬빞 븯怨, 꽭룷 궡뿉 뱾뼱媛꽌 옄떊씠 吏곸젒 諛쒗쁽릺嫄곕굹, 샊 寃고븿 쑀쟾옄쓽 諛쒗쁽쓣 빐븯뿬빞 븳떎. 쑀쟾옄쓽 쟾떖쓣 쐞빐꽌뒗 옱議고빀 諛붿씠윭뒪굹 naked DNA 벑씠 궗슜맂떎.

Ex vivo 쑀쟾옄 쟾떖 vs. in vivo 쑀쟾옄 쟾떖

쑀쟾옄移섎즺젣뒗 쑀쟾옄媛 꽭룷 궡濡 쟾떖릺뒗 쐞移섏뿉 뵲씪꽌 ex vivo 移섎즺젣 in vivo 移섎즺젣濡 굹늻뼱吏꾨떎. Ex vivo 쑀쟾옄移섎즺젣쓽 寃쎌슦 泥댁쇅뿉꽌 쑀쟾옄瑜 듅젙 꽭룷뿉 룄엯븯뿬 利앹떇떆궓 썑뿉 씠 꽭룷(gene-modified cells)瑜 솚옄쓽 泥대궡濡 닾뿬븳떎. 以꾧린꽭룷, T-꽭룷, 뿰怨⑥꽭룷, 닔吏긽꽭룷 벑씠 泥댁쇅 쑀쟾옄 룄엯쓣 쐞븯뿬 궗슜맂떎. 씠 諛⑸쾿 紐⑺몴 씠쇅쓽 옣湲곕굹 議곗쭅씠 臾댁옉쐞 븯寃 諛섏쓳븯뿬 깮湲곕뒗 off target 슚怨쇰 以꾩씪 닔 엳뒗 옣젏씠 엳떎. 삉븳 諛붿씠윭뒪 踰≫꽣瑜 吏곸젒 泥대궡뿉 二쇱엯븷 븣 깮湲곕뒗 硫댁뿭諛섏쓳룄 理쒖냼솕떆궗 닔 엳떎. 二쇱엯 쟾뿉 삎吏덉쟾솚 꽭룷쓽 湲곕뒫 룊媛媛 媛뒫븯湲 븣臾몄뿉 뭹吏덇由ъ 슚뒫솗蹂닿 슜씠븯떎(Lee, 2016).

In vivo 移섎즺젣쓽 寃쎌슦 쟾븯怨좎옄 븯뒗 쑀쟾옄瑜 뵆씪뒪 誘몃뱶굹 諛붿씠윭뒪 벑쓽 踰≫꽣뿉 꽔 썑 씠 踰≫꽣瑜 솚옄뿉寃 닾뿬븯뒗 諛⑹떇씠떎. 씠 諛⑸쾿 꽭룷쓽 異붿텧, 삎吏덉쟾솚, 諛곗뼇 벑쓽 泥댁쇅議곗옉씠 븘슂 뾾湲 븣臾몄뿉 젣젣쓽 以鍮꾩뿉 떆媛꾧낵 鍮꾩슜쓣 以꾩씪 닔 엳떎. 洹몃윭굹 吏곸젒닾뿬濡 씤븯뿬 off target 슚怨쇨 諛쒖깮븷 媛뒫꽦씠 議댁옱븯怨 쑀쟾옄 슫諛섏껜 諛붿씠윭뒪 옄泥닿 硫댁뿭諛섏쓳쓣 쑀諛쒗븯뿬 遺옉슜씠 諛쒖깮븷 닔 엳떎. 쑀諛쒕맂 硫댁뿭諛섏쓳 移섎즺슚怨쇰 媛먯냼떆궗 닔룄 엳떎.

Ex vivo 諛⑹떇씠뱺 in vivo 諛⑹떇씠뱺 쑀쟾옄移섎즺젣쓽 쑀슚꽦씠 솗蹂대릺젮硫 쑀쟾옄媛 꽭룷 궡濡 쟾떖릺怨 삉 쟻젅엳 諛쒗쁽릺뼱빞 븯誘濡, 쑀쟾옄 쟾떖泥 湲곗닠 쑀쟾옄移섎즺젣 媛쒕컻뿉꽌 媛옣 빑떖쟻씤 湲곗닠 以묒쓽 븯굹씠떎(Seo et al., 2015; Lee, 2016).

쑀쟾옄移섎즺쓽 긽씠 릺뒗 꽭룷

泥댁꽭룷 쑀쟾옄移섎즺뒗 깮떇怨 遺꾪솕 愿젴씠 엳뒗 깮떇꽭룷, 諛곗슦옄꽭룷, 誘몃텇솕以꾧린꽭룷瑜 젣쇅븳 떎瑜 꽭룷濡 쑀쟾옄瑜 쟾떖븳떎. 뵲씪꽌 쑀쟾쟻 蹂솕뒗 솚옄 媛쒖씤뿉寃뚮쭔 援븳릺怨 썑넀뿉寃 쑀쟾릺吏 븡뒗떎. 씠뿉 뵲씪 DNA瑜 씠슜븯뿬 吏덈퀝쓣 移섎즺븯怨좎옄 븷 븣, 泥댁꽭룷 쑀쟾옄移섎즺 諛⑸쾿 湲곗큹뿰援щ굹 엫긽뿰援 紐⑤몢뿉꽌 嫄곗쓽 遺遺꾩쓣 李⑥븳떎.

깮떇꽭룷 쑀쟾옄移섎즺뒗 湲곕뒫쟻씤 쑀쟾옄瑜 깮떇꽭룷뿉 룄엯븯뿬 쑀쟾쟻씤 蹂삎(modification)쓣 媛븯뒗 씪씠떎. 뵲씪꽌 珥덈옒릺뒗 쑀쟾쟻씤 蹂솕뒗 썑넀뿉寃 쟾떖맂떎. 遺遺꾩쓽 援媛뿉꽌뒗 깮떇꽭룷 쑀쟾옄移섎즺 뿰援щ 湲덉븯怨 엳떎. 洹몃윭굹 씤媛꾩쓽 쑀쟾옄 蹂삎뿉 븳 援ъ껜쟻씤 젣븳씠 뾾뒗 援媛룄 엳떎.

쑀쟾옄 쟾떖湲곗닠 - 踰≫꽣(vector)

쑀쟾옄 쟾떖湲곗닠 겕寃 3媛吏씤뜲 臾쇰━쟻, 솕븰쟻, 깮臾쇳븰쟻 쟾떖湲곗닠濡 援щ텇맂떎.

泥レ㎏, 臾쇰━쟻씤 諛⑸쾿뿉꽌뒗 쑀쟾옄瑜 諛붿씠윭뒪泥섎읆 떎瑜 쟾떖泥닿 뾾씠 뵆씪뒪誘몃뱶 떒룆 긽깭(naked plasmid)濡 닾뿬븳떎. 쑀쟾臾쇱쭏쓣 꽭룷 궡濡 닾엯븯湲 쐞븯뿬 쟾湲곗쿇怨듬쾿(electroporation)쓣 궗슜븯湲곕룄 븯뒗뜲, 쟾湲곗쟻 옄洹뱀쑝濡 꽭룷留됱뿉 씪떆쟻쑝濡 援щ찉쓣 슟뼱꽌 쑀쟾옄瑜 쟾떖븳떎. 洹 쇅뿉 쑀쟾옄珥(gene gun), 珥덉쓬뙆泥쒓났踰(sonoporation), 옄湲곗옣 씠슜 二쇱엯(magnetofaction)怨 媛숈 諛⑸쾿쓣 궗슜븯湲곕룄 븳떎.

몮吏, 솕븰쟻씤 湲곗닠 由ы룷넑怨 媛숈 怨좊텇옄瑜 씠슜븯뿬 쑀쟾옄瑜 媛먯떥怨, 씠瑜 깮泥 궡뿉 닾뿬븯뿬 꽭룷쓽 깘떇옉슜(endocytosis)쑝濡 꽭룷 궡뿉 룄떖떆궎뒗 湲곗닠씠떎. 吏吏덉냼옱瑜 쟾떖泥대줈 궗슜븯뒗 lipofection 諛⑸쾿씠 쓷엳 궗슜릺怨 엳떎.

臾쇰━쟻, 솕븰쟻 諛⑸쾿怨 媛숈 鍮꾨컮씠윭뒪꽦 踰≫꽣뒗 諛붿씠윭뒪媛 泥대궡濡 쑀엯릺吏 븡쑝誘濡 硫댁뿭諛섏쓳쑝濡 씤븳 뵾빐媛 쟻怨, 깮궛怨쇱젙씠 鍮꾧탳쟻 媛꾨떒븯뿬 궙 鍮꾩슜쑝濡 웾깮궛씠 媛뒫븯떎뒗 옣젏쓣 媛吏꾨떎. 洹몃윭굹 鍮꾨컮씠윭뒪꽦 踰≫꽣뒗 쑀쟾옄쟾떖 슚쑉씠 궙怨 諛쒗쁽씠 씪떆쟻씠씪뒗 寃껋씠 떒젏쑝濡 吏쟻릺뼱 諛붿씠윭뒪 踰≫꽣瑜 留롮씠 궗슜븳떎(Lee, 2016). 鍮꾨컮씠윭뒪꽦 쑀쟾옄쟾떖 諛⑸쾿쑝濡 媛옣 留롮씠 궗슜릺뒗 寃껋 naked plasmid (naked DNA)씠떎. 씠 諛⑸쾿 議곗쭅뿉 諛붾줈 DNA瑜 닾뿬븯뿬 쑀쟾옄媛 諛쒗쁽릺룄濡 븳떎. 諛붿씠윭뒪 踰≫꽣뿉 鍮꾪븯뿬 쑀쟾옄 諛쒗쁽 젙룄媛 궙쑝硫 닾뿬媛 媛뒫븳 遺쐞룄 젣븳쟻씠떎.

꽭 踰덉㎏씤 깮臾쇳븰쟻씤 諛⑸쾿 諛붿씠윭뒪瑜 씠슜븯뒗뜲 諛붿씠윭뒪뿉 썝븯뒗 쑀쟾옄瑜 궫엯븯뿬 쑀쟾옄 옱議고빀 諛붿씠윭뒪瑜 留뚮뱾怨 씠瑜 깮泥 궡濡 닾뿬븯뒗 諛⑹떇씠떎(Seo et al., 2015). 諛붿씠윭뒪뒗 옄떊씠 媛吏 媛먯뿼꽦 뜒遺꾩뿉 닕二쇱꽭룷 궡濡 슜씠븯寃 移⑦닾븳떎. 닕二쇱꽭룷 궡濡 移⑦닾븳 썑, 媛먯떥怨 엳뜕 쇅뵾瑜 踰쀪퀬 쑀쟾臾쇱쭏쓣 꽭룷 궡濡 諛⑹텧븯怨 쑀쟾옄瑜 諛쒗쁽떆궓떎. 씠윭븳 諛붿씠윭뒪쓽 꽦吏덉쓣 씠슜븯뒗 寃껋씠 諛붿씠윭뒪 踰≫꽣씠떎. 踰≫꽣濡 궗슜릺뒗 몴쟻씤 諛붿씠윭뒪濡쒕뒗 븘뜲끂諛붿씠윭뒪(adenovirus), 븘뜲끂뿰愿諛붿씠윭뒪(adeno-associated virus (AAV)), 뿤瑜댄럹뒪諛붿씠윭뒪(herpes simplex virus (HSV)), 젋떚諛붿씠윭뒪(lentivirus), 諛깆떆땲븘諛붿씠윭뒪(vaccinia virus) 벑씠 엳떎. 踰≫꽣슜쑝濡 궗슜릺뒗 諛붿씠윭뒪뒗 遺遺 蹂묒썝꽦씠 젣嫄곕릺怨, 꽭룷 궡뿉꽌 옄媛 蹂듭젣媛 遺덇뒫븯룄濡 젣옉맂 寃껊뱾씠떎.

븘뜲끂諛붿씠윭뒪뒗 吏湲덇퉴吏 媛옣 留롮씠 궗슜릺뒗 諛붿씠윭뒪씠떎. 븘뜲끂諛붿씠윭뒪뒗 蹂묐룆꽦씠 媛뺥븳 諛붿씠윭뒪濡쒖꽌 怨좎뿴쓣 룞諛섑븯뒗 紐⑷컧湲곗 씤썑렪룄뿼, 쑀뻾꽦 媛곴껐留됱뿼, 異쒗삁꽦 諛⑷킅뿼 벑쓣 씪쑝궓떎. 踰≫꽣濡 궗슜릺뒗 븘뜲끂諛붿씠윭뒪뒗 Ad2, Ad5媛 몴쟻씠떎. 쟾떖슚쑉씠 醫뗪퀬 遺꾩뿴 샊 誘몃텇뿴꽭룷뿉 씠슜씠 媛뒫븯떎. 硫댁뿭諛섏쓳 쑀룄媛 臾몄젣媛 릺뿀쑝굹 E2B 媛숈 硫댁뿭諛섏쓳 愿젴씤옄瑜 젣嫄고븯뒗 끂젰쑝濡 留롮씠 媛쒖꽑릺뿀떎. 뿬윭 媛吏 醫낅쪟쓽 븫, 삊떖利, 愿긽룞留μ쭏솚 벑쓽 엫긽뿰援ъ뿉 궗슜릺怨 엳떎.

븘뜲끂뿰愿諛붿씠윭뒪(AAV)뒗 옉 諛붿씠윭뒪濡 씤媛꾩쓣 媛먯뿼떆궎吏留, 硫댁뿭諛섏쓳쓣 留ㅼ슦 빟븯寃 씪쑝궎硫 吏덈퀝쓣 쑀諛쒗븯吏 븡뒗떎. 쑀쟾옄移섎즺 踰≫꽣濡쒖꽌 AAV뒗 遺꾩뿴꽭룷, 誘몃텇뿴꽭룷 紐⑤몢瑜 媛먯뿼떆궎硫 닕二쇨쾶냸뿉 븿엯릺吏 븡 梨꾨줈 吏냽릺뒗뜲, 븿엯맆 寃쎌슦뿉룄 듅젙븳 옣냼뿉留 뱾뼱媛꽌 삁痢≪씠 媛뒫븯떎. 씠윭븳 듅꽦쑝濡 AAV뒗 쑀쟾옄移섎즺쓽 醫뗭 踰≫꽣 썑蹂닿 릺뿀떎. 븳 媛吏 떒젏 쑀쟾泥닿 4.8 kb濡 옉븘꽌 移섎즺슜 쑀쟾옄瑜 꽔湲 쐞빐꽌뒗 몢 쑀쟾泥대 뿰寃고븳 concatemer瑜 留뚮뱶뒗 벑쓽 議곗옉씠 븘슂븯떎. 엫긽떆뿕 긽吏덊솚쑝濡쒕뒗 젅踰꾩꽑泥쒖꽦 쓳븫떆, 뙆궓뒯蹂, 삁슦蹂멊, 븣痢좏븯씠癒, 궘룷꽦꽟쑀利, 留뚯꽦룓뇙꽦吏덊솚 벑 떎닔媛 엳떎.

젅듃濡쒕컮씠윭뒪뒗 쑀쟾옄移섎즺젣 뿰援ъ뿉 珥덉갹湲곕꽣 궗슜릺뿀떎. 젅듃濡쒕컮씠윭뒪뒗 빆썝꽦씠 궙怨, 옣湲곌컙 諛쒗쁽떆궎뒗 옣젏씠 엳쑝굹, 쑀쟾臾쇱쭏쓣 닕二 쑀쟾泥댁뿉 臾댁옉쐞濡 븘臾 쐞移섏뿉굹 궫엯떆궎뒗 臾몄젣媛 엳떎. 쑀쟾옄쓽 媛슫뜲뿉 궫엯맆 寃쎌슦뿉뒗 쑀쟾옄 湲곕뒫쓣 긽떎떆궗 닔 엳怨, 듅젙 쑀쟾옄쓽 議곗젅遺쐞뿉 궫엯맆 寃쎌슦 븫쓣 쑀諛쒗븷 닔룄 엳떎. ADA 寃고븤利, 愿젅뿼, HIV 媛먯뿼, 뵾遺븫, 궃냼븫, 由쇳봽醫 벑쓽 엫긽뿰援ъ뿉 궗슜릺뿀떎.

룺뒪諛붿씠윭뒪(Poxvirus) 踰≫꽣씤 MVA (modified vaccinia virus Ankara)룄 궗씠넗移댁씤씠굹 븫 愿젴 빆썝쓣 깙옱븯뿬 룓븫씠굹, 옣븫 移섎즺뿉 엫긽떆뿕쓣 吏꾪뻾 以묒씠떎. 젋떚諛붿씠윭뒪 踰≫꽣룄 븫빆썝 쑀쟾옄瑜 깙옱븯뿬 룓븫, 궃냼븫 벑쓽 솚옄瑜 긽쑝濡 엫긽떆뿕쓣 吏꾪뻾븯怨 엳떎.

떎瑜 醫낅쪟쓽 諛붿씠윭뒪濡쒕뒗 븫移섎즺뿉 궗슜릺뒗 븫슜빐(oncolytic) 諛붿씠윭뒪媛 엳떎. 씠 슜룄쓽 諛붿씠윭뒪뒗 쑀쟾옄 쟾떖 紐⑹쟻 씠쇅뿉룄 븫꽭룷瑜 媛먯뿼떆耳쒖꽌 吏곸젒쟻쑝濡 븫꽭룷瑜 궗硫몄떆궎怨, 洹 떎쓬 븫꽭룷쓽 빆썝쓣 끂異쒖떆耳쒖꽌 솚옄쓽 硫댁뿭꽭룷瑜 솢꽦솕떆궓떎. 븫슜빐 諛붿씠윭뒪뒗 븫꽭룷뿉꽌留 利앹떇씠 媛뒫븯룄濡 議곗옉릺뼱 엳뼱꽌 븫꽭룷瑜 꽑깮쟻쑝濡 궗硫몄떆궓떎. 옒 븣젮吏 븫슜빐 諛붿씠윭뒪濡쒕뒗 2015뀈 誘멸뎅 FDA 듅씤쓣 쉷뱷븳 쓳깋醫 移섎즺젣씤 븫젨(Amgen)쓽 엫由ъ쭅(Imlygic)씠 엳뒗뜲 뿤瑜댄럹뒪諛붿씠윭뒪瑜 빟룆솕떆耳쒖꽌 留뚮뱺 寃껋씠떎. 씠 븫슜빐 諛붿씠윭뒪뱾 븫꽭룷瑜 怨⑤씪꽌 궡긽떆궎怨, 궡긽맂 븫꽭룷 궡쓽 븫빆썝쓣 쇅遺뿉 끂異쒖떆耳쒖꽌 硫댁뿭꽭룷瑜 쑀룄, 솢꽦솕떆궡쑝濡 蹂듯빀쟻씤 빆븫슚怨쇰 諛쒗쐶븳떎. 援궡뿉꽌 媛쒕컻맂 떊씪젨쓽 럺궗踰(Pexa-Vec)룄 븫슜빐 諛붿씠윭뒪씤뜲 媛꾩븫솚옄瑜 긽쑝濡 湲濡쒕쾶 엫긽 3긽쓣 吏꾪뻾 以묒씠떎. 罹먮굹떎쓽 삩肄붾━떛 諛붿씠삤뀓(Oncolytics Biotech, Inc.)쓽 젅삤由ъ떊(Reolysin) 痍뚯옣븫, 궃냼븫 벑 뿬윭 븫醫낆쓣 긽쑝濡 엫긽떆뿕쓣 븯怨 엳떎. 떎瑜 썑蹂대줈뒗 샇二쇱쓽 鍮꾨씪由ы떛뒪궗(Viralytics Ltd.)媛 肄뺤궗궎諛붿씠윭뒪(Coxackievirus)씤 移대컮깮(Cavatak)쓣 誘멸뎅 뵒뿏뿉씠듃由뒪궗(DNAtrix, Inc.)媛 븘뜲끂諛붿씠윭뒪씤 DNX-2401쓣 엫긽떆뿕 以묒씠떎(Choi, 2017).

쑀쟾옄移섎즺젣쓽 엫긽媛쒕컻怨 떆뙋 듅씤

쑀쟾쟻씤 寃고븿쓣 吏땶 궗엺뿉寃 쇅遺쓽 젙긽 쑀쟾옄瑜 꽔뼱꽌 移섎즺븯옄뒗 쑀쟾옄移섎즺뒗 1972뀈룄뿉 Friedmann怨 Robin씠 泥섏쓬쑝濡 援ъ껜쟻쑝濡 젣븞븯떎怨 蹂 닔 엳떎(Friedmann and Robin, 1972).

쑀쟾옄移섎즺뿉 븳 엫긽뿰援щ뒗 1990뀈뿉 뱾뼱꽌 泥섏쓬쑝濡 듅씤릺뿀떎. 긽솚옄뒗 꽕 궡쓽 Ashanti DeSilva濡 씗洹吏덊솚씤 Adenosine Deaminase (ADA) 寃고븤 以묒쬆蹂듯빀硫 뿭寃고븤利(ADA-SCID)쑝濡 ADA 슚냼媛 寃고븤릺뼱 떖媛곹븳 硫댁뿭泥닿퀎寃고븤쓣 寃り퀬 엳뿀떎. 씠 吏덊솚 硫댁뿭湲곕뒫쓽 븯濡 臾닿퇏 bag뿉꽌 궡븘媛빞 븯湲 븣臾몄뿉 bubble-bag disease씪怨좊룄 遺덈┛떎. 씠 솚옄濡쒕꽣 諛깊삁援щ 梨꾩랬븳 썑, 젙긽 ADA 쑀쟾옄瑜 궫엯븯怨, 씠 꽭룷濡쒕꽣 ADA 솢꽦 깮꽦쓣 솗씤븳 썑뿉 솚옄뿉寃 릺룎젮二쇱뿀떎. 씠 怨쇱젙쓣 諛섎났븳 썑뿉 솚옄쓽 硫댁뿭泥닿퀎뒗 bubble bag씠 븘슂 뾾쓣 젙룄濡 쉶蹂듬릺뿀떎(Blaese et al., 1995).

쑀쟾옄移섎즺젣 뿰援щ뒗 諛붿씠윭뒪瑜 쑀쟾옄 쟾떖泥대줈 궗슜븯硫댁꽌 씗洹쑀쟾蹂 遺꾩빞뿉꽌遺꽣 癒쇱 떆옉릺뿀吏留 븫쓣 鍮꾨’븳 떎瑜 吏덊솚쑝濡 긽씠 솗옣릺뿀떎. 1993뀈 떎삎꽦 援먯븘醫(glioblastoma multiforme) 솚옄瑜 긽쑝濡 씤뒓由곗쑀궗꽦옣씤옄 븞떚꽱뒪 RNA瑜 씠슜븳 엫긽떆뿕씠 닔뻾릺뿀떎(Trojan et al., 1993).

1992뀈뿉뒗 ADA-SCID 엫긽떆뿕쓣 諛쏅뜕 뵾뿕옄 뼱由곗씠 10紐 以 2紐낆뿉寃뚯꽌 諛깊삁蹂 쑀궗利앹긽씠 굹굹꽌 엫긽떆뿕씠 씪떆쟻쑝濡 以묐떒릺뒗 씪씠 諛쒖깮븯湲곕룄 뻽떎. 1999뀈뿉뒗 18꽭쓽 Jesse Gelsinger媛 ornithine transcarbamylase 寃고븤利 쑀쟾옄移섎즺瑜 諛쏅떎媛 닲吏뒗 궗怨좉 諛쒖깮븯뿬, 誘멸뎅 FDA뒗 엫긽떆뿕쓣 以묐떒 議곗튂븯떎. 씠 솚옄뒗 젙긽 쑀쟾옄瑜 媛吏뒗 븘뜲끂諛붿씠윭뒪 踰≫꽣瑜 二쇱엯諛쏆 썑 4씪留뚯뿉 諛붿씠윭뒪濡 씤븳 怨쇰룄븳 硫댁뿭諛섏쓳 븣臾몄뿉 궗留앺븯떎. 2000뀈 3썡뿉뒗 愿긽룞留μ쭏솚쓣 移섎즺븯湲 쐞븯뿬 vascular endothelium growth factor-2 (VEGF2)瑜 닾뿬븯뒗 엫긽떆뿕뿉꽌 궗吏삁愿 넻利앹쓽 臾몄젣媛 諛쒖깮븯뿬 떎떆 FDA뿉꽌 엫긽떆뿕 以묐떒씠 寃곗젙릺뿀떎. 씠븣뒗 諛붿씠윭뒪媛 븘땶 鍮꾧탳쟻 븞쟾븯떎怨 뿬寃⑥쭊 naked plasmid 삎깭濡 쑀쟾옄瑜 삁愿닾뿬濡 쟾떖븯뿀떎. 씠윭븳 씪濡 씤븯뿬 쑀쟾옄移섎즺뒗 븘吏 씠瑜대떎뒗 遺젙쟻씤 湲곕쪟媛 씪떆쟻쑝濡 삎꽦릺뿀怨, 誘멸뎅 FDA뒗 쑀쟾옄移섎즺뿉 빐꽌 쑄由ъ 젅李⑥뿉 븯뿬 떊以묓븯寃 옱룊媛瑜 븯寃 릺뿀떎. 珥덇린뿉 븘뜲끂諛붿씠윭뒪 踰≫꽣瑜 궗슜븳 엫긽떆뿕뿉꽌 遺옉슜씠 씪뼱굹湲곕룄 뻽吏留 씠썑뿉 젋떚諛붿씠윭뒪 踰≫꽣, AAV 踰≫꽣媛 媛쒕컻릺硫댁꽌 슚뒫怨 븞쟾꽦씠 뼢긽릺뿀떎. 삉븳 쟻젅븳 엫긽뵒옄씤怨 뜑遺덉뼱 쑀쟾옄移섎즺뿉 쟻빀븳 吏덊솚씠 꽑젙릺硫댁꽌 쑀쟾옄移섎즺 뿰援щ뒗 떎떆 솢諛쒗빐議뚮떎.

2002뀈 伊먯떎뿕뿉꽌 궖꽭룷鍮덊삁利(Sickle cell disease)씠 쑀쟾옄移섎즺濡 移섎즺맖씠 엯利앸릺뿀떎. 룎뿰蹂씠 HbS쓽 以묓빀쓣 留됰뒗 betaA globin 쑀쟾옄瑜 젋떚諛붿씠윭뒪뿉 꽔 떎쓬, 伊 꽦泥 쟻삁援ъ꽭룷뿉꽌 諛쒗쁽떆耳곕뒗뜲, 궖쟻삁援ъ쓽 삎꽦씠 뼲젣릺뒗 寃껋씠 紐낅갚븯寃 굹궗떎(Pawliuk et al., 2001).

엫긽떆뿕쟻 떆룄뿉꽌 뜑 굹븘媛 쑀쟾옄移섎즺젣濡쒖꽌 떆뙋맆 닔 엳뒗 꽭怨 理쒖큹쓽 긽슜솕맂 쑀쟾옄移섎즺젣뒗 以묎뎅뿉꽌 벑옣븯떎. 以묎뎅 蹂닿굔떦援 2003뀈뿉 븘뜲끂諛붿씠윭뒪瑜 湲곕컲쑝濡 븳 몢寃쎈븫 移섎즺젣濡 Gendicine쓣 듅씤븯怨, 2005뀈뿉뒗 븫슜빐 諛붿씠윭뒪씤 Oncorine쓣 鍮꾩씤몢븫 移섎즺젣濡 듅씤븯떎. 떎瑜 쑀쟾옄移섎즺젣濡쒕뒗 2004뀈뿉 씪듃鍮꾩븘뿉꽌 ECHO-7 virus瑜 湲곕컲쑝濡 븳 쓳깋醫 移섎즺젣 RIGVIR媛 듅씤릺뿀怨, 2007뀈뿉 븘由ы뿉꽌 retrovirus 湲곕컲쓽 쑀諛⑹븫, 痍뚯옣븫 諛붿씠윭뒪 移섎즺젣 Rexin-G媛 듅씤릺뿀떎. 洹몃━怨 2011뀈뿉 윭떆븘뿉꽌 plasmid VEGF 湲곕컲쓽 留먯큹룞留μ쭏솚移섎즺젣 Neovasculgen씠 뿀媛릺뿀떎. 洹몃윭굹 씠 젣뭹뱾 湲濡쒕쾶 移섎즺젣濡 씤젙諛쏆 紐삵븯怨 紐⑤몢 옄援 궡뿉꽌留 븳젙쟻쑝濡 궗슜릺뿀떎(Seo et al., 2015).

湲濡쒕쾶 湲곗쓣 異⑹”븯뒗 꽌諛⑹꽭怨 理쒖큹쓽 긽슜솕맂 쑀쟾옄移섎즺젣뒗 2012뀈 꽕뜙뱶뿉꽌 뿀媛맂 湲由щ쿋씪(Glybera, alipogene tiparvovec)씪怨 븷 닔 엳떎. 湲由щ쿋씪뒗 吏떒諛 吏吏덈텇빐슚냼(lipoprotein lipase (LPL)) 쑀쟾옄瑜 媛吏 븘뜲끂뿰愿諛붿씠윭뒪(adeno-associoated virus, AAV)瑜 湲곕컲쑝濡 븳떎. 湲由щ쿋씪뒗 媛議깆꽦 LPL 寃고븤利앹쑝濡 吏諛⑸텇빐瑜 紐삵븯뒗 솚옄뿉寃 AAV1 踰≫꽣瑜 씠슜빐꽌 洹쇱쑁뿉 LPL 쑀쟾옄瑜 吏곸젒 쟾떖븳떎(Scott, 2015).

2015뀈뿉뒗 誘멸뎅쓽 븫젨궗(Amgen)媛 븙꽦뵾遺븫씤 븙꽦 쓳깋醫낆쓣 移섎즺븯뒗 엫由ъ쭅(Imlygic, talimogene laherparepvec 샊 ’T-vec’)쑝濡 誘멸뎅 FDA뿉꽌 뿀媛瑜 諛쏆븯떎. 엫由ъ쭅 herpes simplex virus type 1쓣 씠슜븯뿬 븫꽭룷瑜 궗硫몄떆궎뒗 븫슜빐 諛붿씠윭뒪 媛쒕뀗쓽 移섎즺젣씠떎. 씠 븫슜빐 諛붿씠윭뒪뒗 븫꽭룷 궡뿉꽌 蹂듭젣릺뼱 諛⑹텧릺硫댁꽌 븫꽭룷瑜 꽣듃젮꽌 궗硫몄떆궓떎(Conry et al., 2018).

2016뀈뿉뒗 뒪듃由쇰꺼由ъ뒪(Strimvelis) 뒪씪옄(Spinraza, nusinersen)媛 듅씤릺뿀떎. 湲씫냼뒪誘몄뒪겢씪씤궗(GSK)쓽 뒪듃由쇰꺼由ъ뒪뒗 ADA-SCID 솚옄쓽 移섎즺瑜 쐞빐 쑀읇 European Medicines Agency (EMA)뿉꽌 듅씤쓣 諛쏆븯떎. 솚옄 蹂몄씤쓽 以꾧린꽭룷(CD34+ 議고삁紐⑥꽭룷) 씪遺瑜 遺꾨━빐궡怨 諛붿씠윭뒪 踰≫꽣瑜 씠슜빐 嫄닿컯븳 ADA 쑀쟾옄쓽 copy瑜 씠 以꾧린꽭룷뿉 궫엯븯떎. 씠뼱꽌 젙긽쟻씤 ADA媛 諛쒗쁽릺뒗 以꾧린꽭룷瑜 솚옄뿉寃 릺룎젮二쇰뒗 怨쇱젙쓣 嫄곗낀떎. 씠 諛⑹떇 꽭룷瑜 湲곕컲쑝濡 븳 솚옄 媛쒖씤뿉 븳 留욎땄삎 移섎즺씠떎(Stirnadel-Farrant et al., 2018).

뒪씪옄뒗 誘멸뎅 븘씠삤땲뒪뙆留덉뒋떚而ъ쫰(Ionis Pharmaceuticals)媛 媛쒕컻뻽뒗뜲 2016뀈 12썡 誘멸뎅 FDA뿉꽌 泥숈닔꽦 洹쇱쐞異뺤쬆(Spinal Muscular Atrophy (SMA)) 移섎즺젣濡 듅씤쓣 쉷뱷븯떎. 꽭怨 理쒖큹쓽 RNA 移섎즺젣濡 湲곕줉릺뒗뜲 湲곗〈 移섎즺젣媛 젒洹쇳븯湲 옒뱺 pre-mRNA瑜 寃⑤깷븳떎. 泥숈닔꽦 洹쇱쐞異뺤쬆 솚옄뒗 SMN1 쑀쟾옄쓽 룎뿰蹂씠굹 寃곗떎濡 씤븯뿬, 슫룞떊寃쎌꽭룷쓽 嫄닿컯怨 湲곕뒫쓣 쑀吏븯뒗 SMN 떒諛깆쭏(깮議 슫룞떊寃쎌꽭룷 떒諛깆쭏)쓣 異⑸텇엳 깮궛븯吏 紐삵븳떎. SMN2 쑀쟾옄뒗 SMN1 쑀쟾옄쓽 諛깆뾽 뿭븷쓣 븯吏留, SMN2 쑀쟾옄쓽 SMN 떒諛깆쭏 깮궛웾 10%뿉 遺덇낵븯뿬 遺議깊븯떎. 뒪씪옄뒗 SMN2 쑀쟾옄 pre-mRNA쓽 씤듃濡 7쓽 ISS-N1 쐞移섏뿉 寃고빀븯뿬 full length SMN2 mRNA瑜 깮꽦븯룄濡 쑀룄븯뿬 SMN 떒諛깆쭏쓽 깮궛웾쓣 利앷떆궓떎(Lee, 2017a; Paton, 2017; Spinraza homepage, 2018).

2017뀈뿉뒗 3醫낆쓽 쑀쟾옄移섎즺젣媛 誘멸뎅 FDA쓽 듅씤쓣 諛쏆븯떎.

끂諛뷀떚뒪궗(Novartis)쓽 궡由ъ븘(Kymriah, tisagenlecleucel)뒗 꽭怨 理쒖큹쓽 궎硫붾씪 빆썝 닔슜泥 T 꽭룷 移섎즺젣(Chimeric antigen receptor T cell (CAR-T))濡 誘멸뎅 FDA뿉꽌 2017뀈 8썡 듅씤쓣 諛쏆븯떎. 궡由ъ븘뒗 솚옄쓽 T 꽭룷瑜 梨꾩랬븳 뮘뿉, 몴硫댁뿉 CD19 빆썝쓣 媛吏 諛깊삁蹂묒꽭룷瑜 몴쟻쑝濡 궪怨 궗硫몄떆궎룄濡 븳 궎硫붾씪 빆썝 닔슜泥 떒諛깆쭏쓣 諛쒗쁽븯뒗 쑀쟾옄瑜 T 꽭룷뿉 룄엯븳 썑뿉, 씠瑜 떎떆 솚옄뿉寃 二쇱엯븯硫 씠 꽭룷媛 븫꽭룷瑜 怨듦꺽븯뒗 썝由ъ씠떎. 씠 媛숈씠 CAR-T뒗 솚옄 留욎땄삎 移섎즺젣떎. 궡由ъ븘뒗 遺덉쓳꽦씠嫄곕굹 理쒖냼 2踰 씠긽 옱諛쒗븳 25꽭 씠븯쓽 B 꽭룷 쟾援 湲됱꽦 由쇳봽援ъ꽦 諛깊삁蹂 솚옄瑜 쐞븳 移섎즺젣濡 듅씤릺뿀떎. 끂諛뷀떚뒪뒗 궡由ъ븘瑜 꽦씤 옱諛쒖꽦 삉뒗 遺덉쓳꽦 誘몃쭔꽦 嫄곕 B 꽭룷 由쇳봽醫 벑뿉 븳 異붽쟻 듅씤쓣 吏꾪뻾 以묒씠떎. 媛옣 쓷븳 遺옉슜 궗씠넗移댁씤 諛⑹텧 利앺썑援(cytokine release syndrome)씤뜲, 빟 젅諛섏쓽 솚옄뱾뿉寃뚯꽌 굹궗쑝굹 利앹긽씠 씪떆쟻씠뿀怨 移섎즺媛 媛뒫뻽떎(Lee, 2017b; Liu et al., 2017).

湲몃━뼱뱶궗(Gilead Science)뿉 쓽빐 씤닔맂 移댁씠듃뙆留(Kite Pharma)쓽 삁뒪移댄(Yescarta, axicabtagene ciloleucel)媛 誘멸뎅 FDA뿉꽌 2017뀈 8썡 듅씤릺뿀뒗뜲 CAR-T 移섎즺젣濡쒖꽌 몢 踰덉㎏씠떎. 뿉뒪移댄뒗 솚옄쓽 T 꽭룷瑜 泥댁쇅뿉꽌 쑀쟾옄議곗옉븯뿬 CD28怨 CD3-zeta co-stimulatory domains媛 뿰寃곕맂 anti-CD19 CAR T-꽭룷濡 留뚮뱺떎. 씠 꽭룷뒗 떎떆 솚옄뿉寃 닾뿬릺硫 CD19瑜 諛쒗쁽븯뒗 몴쟻 븫꽭룷瑜 씤떇븯怨 젣嫄고븳떎. Anti-CD19 CAR T-꽭룷媛 CD19瑜 諛쒗쁽븯뒗 몴쟻 븫꽭룷 寃고빀릺硫 CD28怨 CD3-zeta co-stimulatory domains媛 븯瑜섏쓽 떊샇쟾떖뿰뇙瑜 솢꽦솕떆궓떎. 洹몃윭硫 T 꽭룷媛 솢꽦솕릺怨 利앹떇릺硫, 궗씠넗移댁씤쓣 諛⑹텧븯硫댁꽌 CD19瑜 諛쒗쁽븯뒗 꽭룷瑜 二쎌씠寃 맂떎. 삁뒪移댄뒗 쟾떊 슂踰뺤쓣 諛쏆 긽깭씤 誘몃쭔꽦 嫄곕 B 꽭룷 由쇳봽醫(DLBCL), 썝諛쒖꽦 醫낃꺽룞 嫄곕 B 꽭룷 由쇳봽醫(PMBCL), 怨좊벑湲 B 꽭룷 由쇳봽醫, 냼룷由쇳봽醫낆뿉꽌 DLBCL濡 쟾솚맂 蹂삎맂 냼룷由쇳봽醫(TFL)쓣 鍮꾨’븳 옱諛쒖꽦 삉뒗 遺덉쓳꽦 嫄곕 B 꽭룷 由쇳봽醫낆쓣 븪뒗 꽦씤 솚옄瑜 긽쑝濡 븳 移섎즺젣濡 듅씤릺뿀(Roberts et al., 2017).

뒪뙆겕 꽭씪벂떛뒪(Spark Therapeutics)궗쓽 윮뒪꽣굹(Luxturna, voretigene neparvovec-rzyl)媛 2017뀈 12썡 쑀쟾옄移섎즺젣濡 誘멸뎅 FDA뿉꽌 듅씤릱떎. 윮뒪꽣굹뒗 씠以묐由쎌쑀쟾옄꽦(biallelic) RPE65 룎뿰蹂씠 뿰愿맂 留앸쭑뵒뒪듃濡쒗뵾(retinal dystrophy)瑜 븪뒗 솚옄瑜 긽쑝濡 떒쉶닾뿬븯뒗 쑀쟾옄移섎즺젣씠떎. RPE65 쑀쟾옄뒗 젙긽쟻씤 떆젰쓣 쐞빐 븘슂븳 슚냼瑜 肄붾뵫븯뒗뜲 룎뿰蹂씠 떆 슚냼쓽 솢꽦씠 媛먯냼븯嫄곕굹 寃곗뿬뤌 떆젰넀긽씠 씪뼱궃떎. 윮뒪꽣 굹뒗 젙긽 PE65 쑀쟾옄瑜 븘뜲끂뿰愿諛붿씠윭뒪 踰≫꽣瑜 씠슜븯뿬 留앸쭑꽭룷뿉 吏곸젒 쟾떖븯뿬 遺議깊븳 쑀쟾옄瑜 蹂댁땐빐二쇰룄濡 븳떎. 윮뒪꽣굹뒗 RPE65 쑀쟾옄 移댄뵾 2媛쒖쓽 蹂씠媛 솗씤릱쑝硫 궡븘엳뒗 留앸쭑꽭룷媛 異⑸텇븳 솚옄뿉寃뚮쭔 닾뿬븷 닔 엳떎. 윮뒪꽣굹뒗 FDA濡쒕꽣 쁺떊移섎즺젣, 씗洹쓽빟뭹쑝濡 슦꽑寃넗 긽쑝濡 吏젙諛쏆븯떎. 삉븳 씗洹냼븘吏덊솚 삁諛 諛 移섎즺瑜 쐞븳 쓽빟뭹 媛쒕컻쓣 옣젮븯뒗 봽濡쒓렇옩 븯뿉 씗洹냼븘吏덊솚 슦꽑寃넗 諛붿슦泥섎 諛쏆븘꽌 떊냽븯寃 듅씤 寃넗瑜 諛쏆쓣 닔 엳뿀떎(Lee, 2017c; Ameri, 2018).

뿬윭 媛吏 쑀쟾옄移섎즺젣媛 씠젃寃 誘멸뎅怨 쑀읇뿉꽌 엲떖븘 듅씤릺硫댁꽌 쑀쟾옄移섎즺젣쓽 뿰援 媛쒕컻씠 꽭怨꾩쟻쑝濡 솗릺뼱媛怨 엳떎. 쑀쟾옄移섎즺젣 媛쒕컻 씠젣 븞젙沅뚯뿉 뱾뼱꽌 솗옣 援硫댁뿉 뱾뼱꽣떎怨 룊媛릺怨 엳떎.

쑀쟾옄移섎즺젣쓽 엫긽媛쒕컻 쁽솴

쑀쟾옄移섎즺 愿젴 븰닠臾명뿄 嫄댁닔(2010-2017)

쑀쟾옄移섎즺젣쓽 媛쒕컻怨 愿젴맂 븰닠臾명뿄 嫄댁닔뒗 Pub-Med (PubMed, 2018)瑜 씠슜븯뿬 遺꾩꽍븯떎. PubMed쓽 advanced search瑜 씠슜븯뿬 寃깋뼱 gene therapy [all field]濡 뿰룄蹂꾨줈 굹늻뼱 2010뀈遺꽣 2017뀈源뚯 寃깋븯떎. 2010뀈 18,161嫄댁뿉꽌 2016뀈 28,225嫄댁쑝濡 쑀쟾옄移섎즺젣 愿젴 臾명뿄 닔媛 뀈媛 빟 1,000뿉꽌 2,000뿬嫄 젙룄濡 袁몄엳 利앷븯떎. 끉臾몄닔쓽 利앷 異붿꽭瑜 蹂 븣 쑀쟾옄移섎즺젣 遺꾩빞쓽 뿰援 媛쒕컻씠 袁몄엳 吏냽쟻쑝濡 꽦옣븯怨 엳뒗 寃껋쑝濡 蹂댁씤떎.

쑀쟾옄移섎즺젣쓽 엫긽떆뿕 듅씤 嫄댁닔(1989-2017)

The Journal of Gene Medicine뿉꽌뒗 꽭怨꾩쟻쑝濡 뿀媛릺嫄곕굹, 吏꾪뻾 以묒씠嫄곕굹, 셿猷뚮맂 엫긽떆뿕 닽옄瑜 吏묎퀎븯뿬 꽭怨 쑀쟾옄移섎즺 엫긽 쁽솴 옄猷(Gene Therapy Clinical Trials Worldwide)瑜 諛쒗몴븯怨 엳떎(Gene Therapy Clinical Trials Worldwide homepage, 2018). 1989뀈 泥섏쓬 쑀쟾옄移섎즺젣 엫긽떆뿕씠 듅씤맂 씠옒濡 2017뀈 11썡源뚯 珥 2,597嫄댁쓽 엫긽떆뿕씠 듅씤릺뿀떎. 2000뀈뿉 뱾뼱꽌 뿰媛 빟 100嫄 젙룄쓽 깉濡쒖슫 쑀쟾옄移섎즺젣 엫긽떆뿕씠 듅씤릺뼱吏怨 엳쑝硫, 2015뀈뿉뒗 169嫄, 2016뀈뿉뒗 118嫄, 2017뀈뿉뒗 132嫄댁쓽 쑀쟾옄移섎즺젣 엫긽뿰援ш 꽭怨꾩쟻쑝濡 듅씤릺뿀떎. 엫긽떆뿕씠 듅씤맂 쑀쟾옄移섎즺젣 data뒗 엫긽떆뿕씠 닔뻾맂 瑜숆낵 援媛, 紐⑺몴븯뒗 쟻쓳利, 궗슜맂 쑀쟾옄 슫諛섏껜, 쟾떖맂 쑀쟾옄삎, 엫긽떆뿕 떒怨, 뿀媛 諛 媛쒖떆맂 엫긽떆뿕 嫄댁닔(1989뀈-2017뀈) 媛숈 湲곗쑝濡 遺꾨쪟븯뿬 吏묎퀎릺怨 엳떎.

瑜숇퀎 쑀쟾옄移섎즺젣 엫긽떆뿕 듅씤 嫄댁닔(1989-2017)

瑜 蹂 엫긽떆뿕 嫄댁닔瑜 蹂대㈃ 珥 2,597嫄 以 븘硫붾━移 瑜숈씠 1,685嫄(64.9%)濡 븬룄쟻씤 떎닔瑜 李⑥븳떎. 洹 떎쓬쑝濡 쑀읇씠 602嫄(23.2%), 븘떆븘媛 168嫄(6.5%), 샇二 34嫄(1.3%), 븘봽由ъ뭅媛 6嫄(0.2%)쓣 李⑥븯떎. 떎援쟻 엫긽떆뿕 102嫄(3.9%)씠뿀떎. 쑀쟾옄移섎즺뒗 Big Pharma媛 留롮씠 룷吏꾪빐 엳뒗 遺곷몃瑜숆낵 쑀읇뿉꽌 嫄곗쓽 떎닔쓽 엫긽떆뿕씠 씠猷⑥뼱吏怨 엳떎.

援媛 蹂 쑀쟾옄移섎즺젣 엫긽떆뿕 듅씤 嫄댁닔(1989-2017)

엫긽떆뿕 듅씤 嫄댁닔瑜 援媛蹂꾨줈 궡렣蹂대㈃ 誘멸뎅씠 1,643嫄(63.3%), 쁺援씠 221嫄(8.5%)쑝濡 젅쟻씤 슦쐞瑜 蹂댁씠怨 룆씪씠 92嫄(3.5%), 以묎뎅씠 84嫄(3.2%)쑝濡 뮘瑜 엲怨 엳떎. 洹 떎쓬쑝濡쒕뒗 봽옉뒪 59嫄(2.3%), 뒪쐞뒪 50嫄(1.9%), 씪蹂 44嫄(1.7%), 꽕뜙뱶 37嫄(1.4%), 뒪럹씤 32嫄(0.5%), 씠깉由ъ븘 28嫄(1.1%), 罹먮굹떎 27嫄(1.0%) 닚씠뿀떎. 븳援 20嫄댁쑝濡(0.8%) 14쐞뿉 삱씪媛 엳떎.

吏덊솚 蹂 쑀쟾옄移섎즺젣 엫긽떆뿕 듅씤 嫄댁닔(1989-2017)

쑀쟾옄移섎즺젣쓽 엫긽떆뿕쓣 쟻쓳利 蹂꾨줈 궡렣蹂대㈃ 醫낆뼇吏덊솚씠 1,688嫄댁쑝濡 쟾泥댁쓽 65%瑜 李⑥븳떎. 洹 떎쓬쑝濡 떒씪쑀쟾옄꽦 吏덊솚 287嫄(11.1%), 媛먯뿼꽦吏덊솚 182嫄(6.9%), 떖삁愿怨꾩쭏솚 180嫄(6.9%), 떊寃쏀븰쟻吏덊솚 47嫄(1.8%) 닚씠떎. 븞吏덊솚뿉 34嫄(1.3%), 뿼利앹꽦吏덊솚뿉 15嫄(0.6%)씠 엳쑝硫, 湲고 吏덊솚뿉 58嫄(2.2%)쓽 엫긽떆뿕씠 듅씤릺뿀떎(Table 1).

Indications Addressed by Gene Therapy Clinical Trials (1989-2017)

 IndicationsGene therapy clinical trials

Number%
Cancer diseases1,68865.0
Cardiovascular diseases1806.9
Gene marking501.9
Healthy volunteers562.2
Infectious diseases1827.0
Inflammatory diseases150.6
Monogenic diseases28711.1
Neurological diseases471.8
Ocular diseases341.3
Others582.2

Total2,597100.0

Source: http://www.abedia.com/wiley/indications.php (updated Nov. 2017)


醫낆뼇吏덊솚 쑀쟾옄移섎즺 遺꾩빞뿉꽌 엫긽뿰援ш 媛옣 솢諛쒗븯寃 씠猷⑥뼱吏怨 엳뒗 遺꾩빞씠떎. 궃냼븫, 쟾由쎌꽑븫, 룓븫, 쑀諛⑹븫, 뇤醫낆뼇 벑 떎뼇븳 븫뿉 엫긽떆뿕씠 吏꾪뻾 以묒씠떎. 븫쓽 移섎즺뿉뒗 諛붿씠윭뒪꽦 踰≫꽣媛 留롮씠 궗슜릺怨 엳쑝硫 醫낆뼇遺쐞뿉 吏곸젒 二쇱엯븯뒗 삎깭濡 궗슜맂떎. 븫꽭룷瑜 젣뼱븯湲 쐞빐꽌 cell suicide, cell death, growth inhibition, tumor suppression怨 oncolysis 벑쓽 湲곗쟾쓣 궗슜븳떎.

쑀쟾吏덊솚쑝濡쒕뒗 옒踰꾩뵪꽑泥쒖꽦 쓳븫떆, 궘룷꽦꽟쑀利, 吏떒諛깆吏덈텇빐슚냼 寃고븤, ADA 寃고븤옣븷, 삁슦蹂 벑뿉 븯뿬 엫긽뿰援ш 뻾빐吏怨 엳떎. 쑀쟾옄 슫諛섏껜濡쒕뒗 AAV, 젅듃濡쒕컮씠윭뒪, 由ы룷넑 벑씠 궗슜맂떎. 닾뿬諛⑸쾿쑝濡쒕뒗 二쇰줈 삁愿 二쇱엯쑝濡 씠猷⑥뼱吏뒗뜲, 긽 議곗쭅씤 븞議곗쭅뿉 吏곸젒 二쇱궗븯뒗 寃쎌슦룄 엳뿀떎. 떒씪 쑀쟾옄꽦 吏덊솚쓽 寃쎌슦 寃고븤맂 쑀쟾옄 湲곕뒫쓣 蹂댁땐븿쑝濡쒖뜥 湲곕뒫쓽 蹂듭썝쓣 湲곕븳떎(Peters and Harris, 2018).

媛먯뿼꽦吏덊솚쓽 엫긽뿰援щ뒗 HIV, 媛꾩뿼 벑뿉 븯뿬 씠猷⑥뼱吏怨 엳떎. 쑀쟾옄쟾떖泥대줈뒗 젅듃濡쒕컮씠윭뒪굹 naked plasmid瑜 씠슜븯硫 젙留μ쑝濡 닾뿬맂떎. 옉슜湲곗쟾 硫댁뿭쓣 쑀룄븯뒗 硫댁뿭移섎즺 愿젴씠 엳떎.

떖삁愿怨꾩쭏솚쓽 寃쎌슦뿉뒗 엫긽뿰援ш 愿긽룞留μ쭏솚, 留먯큹룞留μ쭏솚, 떖遺쟾쓣 以묒떖쑝濡 씠猷⑥뼱吏怨 엳떎. 쑀쟾옄슫諛섏껜濡쒕뒗 naked plasmid媛 媛옣 留롪퀬 諛붿씠윭뒪꽦쑝濡쒕뒗 븘뜲끂諛붿씠윭뒪媛 二쇰줈 궗슜릺뒗뜲 닾뿬寃쎈줈뒗 떖옣, 洹쇱쑁, 삁愿 벑뿉 二쇱궗맂떎(Dunbar et al., 2018).

뇤떊寃쎄퀎吏덊솚쓽 엫긽뿰援щ뒗 二쇰줈 뙆궓뒯蹂, 븣痢좏븯씠癒, 떦눊蹂묒꽦 떊寃쎈퀝利앹뿉꽌 씠猷⑥뼱吏怨 엳떎. 궗슜릺뒗 踰≫꽣濡쒕뒗 AAV, 젋떚諛붿씠윭뒪, 젅듃濡쒕컮씠윭뒪, naked plasmid 벑씠 엳떎. 뇤떊寃쎄퀎吏덊솚뿉꽌뒗 빟由ъ옉슜쓣 媛吏뒗 移섎즺 떒諛깆쭏쓣 踰≫꽣媛 諛쒗쁽, 遺꾨퉬븯룄濡 븯뿬 移섎즺슚怨쇰 굹궡룄濡 븳떎. 吏덊솚뿉 뵲씪 닾뿬븯뒗 諛⑹떇씠 떖씪꽌 븣痢좏븯씠癒몃굹 뙆궓뒯蹂묒쓽 寃쎌슦 뇤議곗쭅뿉 二쇱궗븯怨 떦눊蹂묒꽦 떊寃쎈퀝利앹쓽 寃쎌슦 洹쇱쑁뿉 二쇱궗븳떎(Lee, 2016; Hong et al., 2016;Abbasi, 2018; Saudemont et al., 2018; Tosoloni and Smith, 2018).

踰≫꽣 蹂 쑀쟾옄移섎즺젣 엫긽떆뿕 듅씤 嫄댁닔(1989-2017)

엫긽떆뿕 듅씤 嫄댁닔瑜 쑀쟾옄瑜 쟾떖븯뒗 踰≫꽣 蹂꾨줈 援щ텇빐 蹂대㈃ 諛붿씠윭뒪 踰≫꽣媛 떎닔瑜 李⑥븯떎. 몴쟻씤 諛붿씠윭뒪꽦 踰≫꽣濡 adenovirus 521嫄(20.1%), retrovirus 475嫄(18.3%), adeno-associated virus 204嫄(7.9%), lentivirus 196嫄(7.5%), vaccinia virus 127嫄(4.9%) 벑씠 궗슜릺뿀떎. 洹 떎쓬 鍮덈룄濡쒕뒗 herpes simplex virus 93嫄(3.6%), pox virus 70嫄(2.7%), measles virus 13嫄(0.5%) 닚꽌떎. Newcastle disease virus, Poliovirus, Semliki forest virus, Sendai virus, Simian virus, Venezuelan equine encephalitis virus replicon, Vesicular stomatitis virus 벑룄 냼닔쓽 엫긽떆뿕뿉꽌 궗슜릺뿀떎.

鍮꾨컮씠윭뒪꽦 踰≫꽣濡쒕뒗 쑀쟾옄瑜 吏곸젒 쟾떖븯뒗 naked plasmid媛 429嫄(16.5%)쑝濡 媛옣 留롮 닔瑜 李⑥븯떎. RNA transfer룄 48嫄(1.8%)씠 궗슜릺뿀怨 siRNA 궗슜씠 5嫄(0.2%), antisense oligonucleotide 궗슜씠 6嫄(0.2%)씠 엳뿀떎. 吏吏덈쭑쑝濡 쑀쟾臾쇱쭏쓣 媛먯떥꽌 떇꽭룷옉슜쑝濡 쑀쟾옄瑜 쟾떖븯뒗 lipofection룄 117嫄(4.5%)쓣 李⑥븯떎. 洹 쇅뿉 臾쇰━쟻씤 諛⑸쾿쓣 씠슜븯뒗 mRNA electroporation씠 6嫄(0.2%) 엳뿀떎. Listeria monocytogenes, Streptococcus mutans, Vibrio cholerae, Shigella dysenteriae, Salmonella typhimurium 벑怨 媛숈 諛뺥뀒由ъ븘룄 냼닔쓽 엫긽떆뿕뿉 궗슜릺뿀떎.

쑀쟾옄 엯 蹂 쑀쟾옄移섎즺젣 엫긽떆뿕 듅씤 嫄댁닔(1989-2017)

쑀쟾옄移섎즺젣 엫긽떆뿕뿉꽌 쟾떖맂 쑀쟾옄 엯 쟻슜릺뒗 吏덊솚뿉 뵲씪 떎瑜 留뚰겮 醫낅쪟媛 떎뼇븯떎. Antigen씠 498嫄(19.2%), cytokine씠 375嫄(14.4%), receptor媛 301嫄(11.6%)쑝濡 媛옣 留롮씠 궗슜릺뿀떎. 洹 떎쓬쑝濡쒕뒗 寃고븤쑀쟾옄 221嫄(8.5%), growth factor 183嫄(7.0%), tumor suppressor 181嫄(7.0%), suicide gene 175嫄(6.7%), replication inhibitor 96嫄(3.7%), marker 55嫄(2.1%), oncolytic virus 52嫄(2.0%), transcription factor 35嫄(1.3%) 벑씠 궗슜릺뿀떎. 냼닔쓽 寃쎌슦뿉 antisense, cell cycle, hormone, oncogene regulator, porins, ion channels, transporters, ribozyme, siRNA 벑씠 궗슜릺뿀떎.

엫긽떆뿕 떒怨 蹂 쑀쟾옄移섎즺젣 듅씤 쁽솴(1989-2017)

엫긽떆뿕 떒怨 蹂꾨줈 궡렣蹂대㈃ 냼닔쓽 嫄닿컯븳 꽦씤쓣 긽쑝濡 빟臾쇱쓽 泥대궡 씉닔, 遺꾪룷, 궗, 諛곗꽕 벑뿉 븳 옄猷뚮 닔吏묓븯硫댁꽌 븞쟾꽦쓣 룊媛븯뒗 엫긽 젣1긽 떒怨꾩뿉 엳뒗 寃쎌슦媛 1,476嫄댁쑝濡 쟾泥댁쓽 56.8%瑜 李⑥븯떎. 냼洹쒕え쓽 솚옄瑜 긽濡 쟻젙슜웾쓽 踰붿쐞(理쒖쟻 닾뿬웾 벑) 슜踰뺤쓣 룊媛븯뒗 엫긽 젣2긽 뿰援ш 듅씤맂 寃쎌슦뒗 젣1긽怨 젣3긽 샎옱瑜 룷븿븯뿬 39%瑜 李⑥븯떎. 떎쓬 떒怨꾨줈 洹쒕え쓽 솚옄瑜 긽쑝濡 빟臾쇱쓽 쑀슚꽦怨 븞쟾꽦쓣 理쒖쥌쟻쑝濡 寃利앺븯뒗 엫긽 3긽 떒怨꾩뿉 룄떖븳 寃쎌슦뒗 98嫄댁쑝濡 쟾泥댁쓽 빟 4%씠뿀떎. 吏湲덇퉴吏 빟臾쇱쓣 떆뙋븳 썑 遺옉슜쓣 異붿쟻븯뿬 븞쟾꽦쓣 옱怨좏븯뒗 엫긽 젣4긽源뚯 듅씤맂 寃쎌슦뒗 3嫄댁씠뿀떎(Table 2).

Phases of Gene Therapy Clinical Trials (1989-2017)

 PhaseGene therapy clinical trials

Number%
Phase I1,47656.8
Phase I/II54420.9
Phase II44517.1
Phase II/III251.0
Phase III983.8
Phase IV30.1
Single subject60.2

Total2,597100.0

Source: http://www.abedia.com/wiley/phases.php (updated Nov. 2017)


媛곴뎅 蹂닿굔떦援쓽 쑀쟾옄移섎즺젣 洹쒖젣 媛씠뱶씪씤 쁽솴

媛 굹씪留덈떎 湲곗닠媛쒕컻 닔以怨 뿰援ш린諛, 諛붿씠삤/쓽빟뭹 궛뾽 닔以, 쓽猷 씤봽씪 벑쓽 뿬嫄댁뿉꽌 寃⑹감媛 엳뒗 留뚰겮 쑀쟾옄移섎즺젣 媛쒕컻쓽 媛씠뱶씪씤룄 援媛 蹂꾨줈 꽌濡 李⑥씠瑜 蹂댁씤떎. 씠뿉 뜑븯뿬 쑀쟾옄移섎즺젣媛 떎뼇븳 諛⑹떇쑝濡 媛쒕컻릺怨 엳怨 삉븳 愿젴湲곗닠씠 鍮좊Ⅸ 냽룄濡 諛쒖쟾빐媛먯뿉 뵲씪꽌 癒쇱 留뚮뱾뼱吏 媛씠뱶씪씤 떆媛꾩씠 吏궇닔濡 쁽떎쓣 洹쒖젣븯湲곗뿉 臾대━媛 뵲瑜닿쾶 맂떎. 씠뿉 뵲씪 媛곴뎅쓽 洹쒖젣떦援 븰臾몄쓽 吏꾨낫瑜 諛섏쁺븯뿬 깉濡쒖슫 媛씠뱶씪씤쓣 젣젙 샊 媛쒖젙븯怨, 쑀쟾옄移섎즺젣瑜 떖궗븿뿉 엳뼱꽌 쑀뿰븯怨 빀由ъ쟻씤 뙋떒쓣 븷 닔 엳룄濡 끂젰븯怨 엳떎. 媛곴뎅뿉꽌 젣젙맂 쑀쟾옄移섎즺젣 媛씠뱶씪씤 뭹吏덇由, 젣議, 鍮꾩엫긽떆뿕, 엫긽떆뿕, 떆뙋 썑 궗썑愿由ъ뿉 씠瑜닿린源뚯 쟾泥댁쟻씤 怨쇱젙뿉 븳 洹쒖젣 愿由ъ쓽 쓣 젣怨듯븳떎(Seo et al., 2015).

誘멸뎅쓽 쑀쟾옄移섎즺젣 媛씠뱶씪씤: 誘멸뎅뿉꽌뒗 1998뀈 3썡뿉 泥섏쓬쑝濡 Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy媛 굹삩 씠옒濡 2018뀈 6썡 쁽옱源뚯 Cellular & Gene Therapy Guidance 愿젴븯뿬 24媛쒖쓽 guideline씠 젣젙 샊 媛쒖젙릺뼱 諛쒓컙릺뿀떎. 理쒓렐 3뀈 룞븞 꽭룷 諛 쑀쟾옄移섎즺 愿젴맂 9嫄 (2015뀈룄 3嫄, 2016뀈룄 1嫄, 2017뀈룄 5嫄)쓽 깉濡쒖슫 guideline씠 젣젙릺뼱 怨듯룷릺뿀떎(Seo et al., 2015; US FDA homepage. Vaccines, Blood & Biologics, Cellular & Gene Therapy Guidance Documents, 2018). 씠뿉 뜑븯뿬 誘멸뎅 FDA뒗 쑀쟾옄移섎즺젣쓽 뿀媛瑜 썝솢븯寃 븯湲 쐞븯뿬 쑀쟾옄 移섎즺젣 愿젴븳 6媛쒖쓽 깉濡쒖슫 媛씠뱶씪씤쓣 議곕쭔媛 怨듯룷븷 삁젙씠씪怨 븳떎(Terry, 2018).

쑀읇쓽 쑀쟾옄移섎즺젣 媛씠뱶씪씤: 쑀읇뿉꽌뒗 European Medicines Agency (EMA)媛 쑀쟾옄移섎즺젣 愿젴븯뿬 2001뀈뿉 Quality, preclinical and clinical aspects of gene therapy medicinal products瑜 泥섏쓬쑝濡 諛쒓컙븳 씠옒濡 2018뀈 6썡 쁽옱源뚯 11媛쒖쓽 guideline쓣 諛쒓컙븯떎. 씠 媛씠뱶씪씤쓽 젣젙 痍⑥뒗 쑀쟾옄移섎즺젣 媛쒕컻옄뱾씠 떆뙋뿀媛瑜 떊泥븯뒗 以鍮꾨 룙湲 쐞븳떎怨 泥쒕챸릺뿀떎(Seo et al., 2015; European Medicines Agency homepage, Human regulatory, Scientific guidelines, Multidisplinary, Gene therapy, 2018).

슦由щ굹씪쓽 쑀쟾옄移섎즺젣 媛씠뱶씪씤: 슦由щ굹씪 떇뭹쓽 빟뭹븞쟾泥섏뿉꽌룄 쑀쟾옄移섎즺젣 媛쒕컻쓽 꽭怨꾩쟻씤 쓲由꾩뿉 뒫룞쟻쑝濡 泥섑븯怨, 쑀쟾옄移섎즺젣쓽 媛쒕컻쓣 吏썝븯湲 쐞븯뿬 븘옒 媛숈 醫낅쪟쓽 쑀쟾옄移섎즺젣 媛씠뱶씪씤쓣 젣젙븯뿬 떆뻾븯怨 엳떎(Korean FDA homepage, 2018).

  • - 泥⑤떒諛붿씠삤쓽빟뭹 洹쒖젣怨쇳븰 긽떞 궗濡吏-[誘쇱썝씤븞궡꽌]. 2017-12-27

  • - 쑀쟾옄移섎즺젣 鍮꾩엫긽떆뿕 룊媛 媛씠뱶씪씤-[誘쇱썝씤븞궡꽌]. 2017-12-22

  • - 쑀쟾옄移섎즺젣 엫긽떆뿕 媛씠뱶씪씤-吏뿰꽦 씠긽諛섏쓳뿉 鍮꾪븳 솚옄 異붿쟻愿李-[誘쇱썝씤 븞궡꽌]. 2016-10-31

  • - 엫긽떆뿕슜 쑀쟾옄移섎즺젣쓽 듅꽦遺꾩꽍, 젣議 諛 뭹吏덇由 룊媛媛씠뱶-[誘쇱썝씤 븞궡꽌]. 2016-01-01

  • - 꽭룷 · 쑀쟾옄移섎즺젣 珥덇린 엫긽떆뿕 뵒옄씤 媛씠뱶씪씤-[誘쇱썝씤 븞궡꽌]. 2015-11-30

  • - 떊媛쒕뀗 泥⑤떒젣젣 誘쇱썝寃넗瑜 쐞븳 쟾臾멸 옄臾몄뿉 愿븳젅李-[怨듬Т썝 吏移⑥꽌]. 2012-07-31

寃곕줎 諛 끉쓽

理쒓렐 紐 뀈 룞븞 誘멸뎅怨 쑀읇뿉꽌 뿬윭 媛쒖쓽 쑀쟾옄移섎즺젣媛 蹂닿굔떦援쓽 뿀媛瑜 쉷뱷븯떎. 쑀읇 EMA뿉꽌 2012뀈 泥섏쓬 쑀쟾옄移섎즺젣濡 듅씤맂 湲由щ쿋씪뒗 吏굹移섍쾶 넂 빟媛 쟻 솚옄 닔濡 씤븳 떆옣꽦 遺議깆쓣 씠쑀濡 쑀땲걧뼱궗뒗 븘돺寃뚮룄 2017뀈 옱벑濡앹쓣 룷湲고븯湲곕줈 寃곗젙븯떎(Warner, 2017). 洹몃윭굹 湲由щ쿋씪뒗 꽌諛⑹꽑吏꾧뎅뿉꽌 湲濡쒕쾶 닔以쓽 泥 긽슜솕맂 젣뭹쑝濡쒖꽌, 떎瑜 썑냽 쑀쟾옄移섎즺젣 媛쒕컻쓽 臾쇨퀬瑜 듉 寃껋쑝濡 겙 媛移섍 엳뿀떎. 2015뀈 씠썑뿉 誘멸뎅怨 쑀읇뿉꽌 뿰씠뼱 듅씤맂 떎닔쓽 쑀留앺븳 쑀쟾옄移섎즺젣뒗 뼢썑 쑀쟾옄移섎즺젣 떆媛 蹂멸꺽쟻쑝濡 뿴由 寃껋쓣 삁怨좏븯怨 엳떎.

쁽옱 援媛 蹂꾨줈 蹂대㈃ 誘멸뎅씠 쑀쟾옄移섎즺젣 뿰援щ 媛옣 留롮씠 吏꾪뻾븯怨 엳떎. 誘멸뎅怨 쑀읇씠 쑀쟾옄移섎즺젣 뿰援щ 꽑룄븯怨 엳吏留, 씪遺 쑀쟾옄移섎즺젣 遺꾩빞뒗 以묎뎅씠 솢諛쒗븯寃 吏곸씠怨 엳뼱꽌 뼢썑뿉 以묒슂븳 뿭븷쓣 븷 寃껋쑝濡 깮媛곷맂떎(Seo et al., 2015).

洹몃룞븞 슦由щ굹씪룄 留롮 쉶궗뱾씠 쑀쟾옄移섎즺젣 媛쒕컻뿉 쎇뼱 뱾뼱 뿰援щ 븯怨 엳떎. 2018뀈 5썡 7씪 Genetic and Biotechnology News뿉꽌 異쒖떆媛 엫諛뺥븳 꽭怨 쑀留 쑀쟾옄移섎즺젣 25醫(25 Up and Coming Gene Therapies)쓣 꽑諛쒗븯떎. 뿬湲곗뿉 슦由щ굹씪 젣뭹쑝濡쒕뒗 떊씪젨 럺궗踰(Pexa-Vec (Pexastimogene devacirepvec; JX-594))怨 諛붿씠濡쒕찓뱶쓽 VM202媛 삱씪媛붾떎.

떊씪젨쓽 럺궗踰≪ 踰≪떆땲븘 諛붿씠윭뒪瑜 씠슜븯뿬 吏곸젒 븫꽭룷瑜 슜빐떆궎怨, 빆븫硫댁뿭옉슜쓣 옄洹뱁븯뒗뜲 媛꾩꽭룷븫醫(Hepatocellular carcinoma) 移섎즺젣濡 엫긽 3긽 떆뿕 以묒씠떎. 럺궗踰≪ 삉 떎瑜 4醫낆쓽 빆븫젣 蹂묒슜슂踰뺤쑝濡 쟾씠/吏꾪뻾꽦 怨좏삎븫, 媛꾩꽭룷븫醫, 떊옣븫뿉 엫긽 1/2긽 떆뿕以묒씠떎.

諛붿씠濡쒕찓뱶쓽 VM202뒗 HGF728怨 HGF 723쓣 諛쒗쁽븯뒗 naked plasmid 젣젣씠떎. VM202뒗 넻利앹꽦 떦눊蹂묒꽦留 珥덉떊寃쎈퀝利(PDPN, painful diabetic peripheral neuropathy), 떦눊蹂묒꽦 · 뿀삁꽦議깅沅ㅼ뼇(NHU, diabetic foot ulcers), 以묒쬆븯吏뿀삁(CLI, critical limb ischemia)쓣 긽쑝濡 엫긽 3긽, 뿀삁꽦떖옣吏덊솚(IHD, ischemic heart disease)怨 猷④쾶由蹂(洹쇱쐞 異뺤꽦異뺤궘寃쏀솕利, ALS, amyotrophic lateral sclerosis)쓣 긽쑝濡 엫긽 2긽 떆뿕쓣 吏꾪뻾븯怨 엳떎(Philippidis, 2018). 洹 쇅뿉룄 쟾엫긽怨 엫긽 1, 2긽 떒怨꾩뿉 엳뒗 援궡 媛쒕컻 쑀쟾옄移섎즺젣媛 留롮씠 룷吏꾪븯怨 엳뼱꽌 쟾룄媛 諛앸떎.

誘멸뎅 援由쎈낫嫄댁뿰援ъ썝(NIH) 궛븯 US National Library of Medicine뿉꽌 슫쁺븯뒗 ClinicalTrial.gov 궗씠듃뿉 쓽븯硫 2018뀈 6썡 쁽옱 ’gene therapy’濡 寃깋 떆 굹굹뒗 쑀쟾옄移섎즺 愿젴 엫긽뿰援щ뒗 494嫄댁씠硫, 엫긽 3긽 떆뿕씠 吏꾪뻾릺怨 엳뒗 pipeline씠 27媛쒕줈 굹궃떎. 쑀쟾옄移섎즺젣 뿰援ъ쓽 珥덇린뿉뒗 궃移섏븫씠굹 씗洹 쑀쟾吏덊솚씠 二쇱슂 몴쟻씠뿀뒗뜲 씠젣 쟻슜 寃잛씠 븫, 쑀쟾吏덊솚, 留뚯꽦吏덊솚, 媛먯뿼吏덊솚, 떖삁愿怨, 떊寃쎄퀎吏덊솚, 留뚯꽦吏덊솚 벑쑝濡 떎뼇빐吏怨 엳떎(ClinicalTrial.gov homepage, 2018).

쑀쟾옄移섎즺젣쓽 쟻슜긽 븫씠 媛옣 留롮 뿰援щ릺怨 엳쑝硫 洹 떎쓬쑝濡 떒씪 쑀쟾옄吏덊솚씠떎. 떒씪 쑀쟾옄吏덊솚 옉슜湲곗쟾씠 鍮꾧탳쟻 떒닚븯怨 遺遺 씗洹吏덊솚쑝濡 吏젙릺뼱 엳뼱꽌 뿀媛 떆 씗洹吏덊솚쓽빟뭹쑝濡 吏젙맆 닔 엳뼱꽌 꽭젣삙깮怨 씪젙湲곌컙 룆젏뙋留ㅺ텒 솗蹂닿 슜씠븳 寃껋씠 媛쒕컻궗뱾뿉寃 쑀由ы븯寃 옉슜븳떎. 洹몃━怨 삉 떎瑜 以묒슂븳 긽 솚옄쓽 룺씠 꼻뼱 닔슂媛 겙 떖삁愿怨꾩쭏솚씠떎. 솚옄 닔 떆옣洹쒕え瑜 깮媛곹븯硫 씠 遺꾩빞뿉꽌룄 blockbuster 湲됱쓽 쑀쟾옄移섎즺젣 떊빟씠 벑옣븯由щ씪 삁긽맂떎.

2018뀈 6썡 4씪뿉꽌 7씪 궗씠뿉 誘멸뎅 蹂댁뒪꽩뿉꽌 媛쒖턀맂 2018 BIO International Convention (BioUSA)뿉꽌 쑀쟾옄移섎즺젣 媛쒕컻 젙諛쓽븰怨 뜑遺덉뼱 愿떖쓽 以묒떖씠뿀떎. Dr. Scott Gottlieb 誘멸뎅 FDA 援옣 넗濡좏쉶뿉꽌 2022뀈源뚯 誘멸뎅뿉꽌 빟 40媛 젙룄쓽 쑀쟾옄移섎즺젣媛 듅씤맆 寃껋쑝濡 쟾留앸릺硫, 10뀈 씠궡뿉 궖쟻삁援щ퉰삁利앷낵 媛숈 쑀쟾吏덊솚 移섎즺踰뺤쓣 李얘쾶 맆 寃껋씠씪怨 뼵湲됲븯떎. 삉븳 쑀쟾옄移섎즺젣쓽 듅닔꽦쓣 媛먯븞븯뿬 븵쑝濡 뿀媛怨쇱젙뿉 씠쟾怨 떎瑜닿쾶 젒洹쇳븷 寃껋씠硫, 뿀媛怨쇱젙쓣 썝솢븯寃 븯湲 쐞븯뿬 쑀쟾옄移섎즺젣 愿젴븳 6媛쒖쓽 깉濡쒖슫 媛씠뱶씪씤쓣 議곕쭔媛 怨듯룷븷 寃껋씠씪怨 븯떎(Terry, 2018). 씠뒗 誘멸뎅 젙遺媛 쑀쟾옄移섎즺젣쓽 옞옱젰쓣 넂씠 룊媛븯怨 뿀媛瑜 쟾뼢쟻쑝濡 寃넗븯怨 엳쓬쓣 떆궗븳떎.

씠 媛숈 誘멸뎅 FDA쓽 吏곸엫 2018뀈 6썡 27씪 꽌슱뿉꽌 뿴由 湲濡쒕쾶 諛붿씠삤 而⑦띁윴뒪(GBC 2018)뿉꽌 誘멸뎅떇뭹쓽빟援(FDA) 깮臾쇳븰쟻젣젣 룊媛뿰援 꽱꽣(CBER) 議곗쭅泥⑤떒移섎즺젣援(OTAT) 쐧뒯 釉뚮씪씠뼵(Wilson W. Bryan) 諛뺤궗쓽 湲곗“뿰꽕濡 떎떆 븳 踰 솗씤릺뿀떎. 洹몃뒗 “쑀쟾옄移섎즺젣뒗 떖媛곹븳 吏덊솚쓣 移섎즺븯怨 솚옄뱾쓽 궣쓣 諛붽씀뒗 留뚰겮 媛쒕컻怨 뿀媛怨쇱젙뿉꽌룄 떆媛곸쓣 諛붽 븘슂媛 엳떎. 泥 엫긽떆뿕쓣 꽕怨꾪븷 븣 븳 踰덉쑝濡 븞쟾꽦怨 쑀슚꽦 洹쇨굅瑜 닔吏묓빐 諛붾줈 떆뙋源뚯 븷 닔 엳룄濡 븯뒗 諛⑸쾿쓣 怨좊젮빐빞 븯硫, 쑀쟾옄移섎즺젣뒗 媛뺣젰븳 怨쇳븰쟻 洹쇨굅瑜 諛뷀깢쑝濡 븯뒗 留뚰겮 쑀슚꽦 洹쇨굅瑜 젣怨듯븳떎硫 엫긽 1긽留뚯쑝濡쒕룄 듅씤 媛뒫븯룄濡 珥덇린遺꽣 엫긽쓽瑜 李몄뿬떆궎怨 쑀슚꽦 뜲씠꽣 솗蹂댄븯怨 젣議 臾몄젣룄 誘몃━ 鍮꾪빐빞 븷 븘슂븯떎”怨 議곗뼵뻽떎. 洹몃뒗 “誘멸뎅 FDA뒗 꽭룷移섎즺젣, 쑀쟾옄移섎즺젣 벑 泥⑤떒 옱깮쓽빟뭹씠 솚옄뱾뿉寃 媛뒫븳 鍮⑤━ 젣怨듬릺룄濡 洹쒖젣 泥좏룓 븿猿 븞쟾꽦쓣 媛뺥솕븯뒗 젙梨낆쓣 異붿쭊븯怨 엳떎”怨 留먰뻽떎. 삉븳 “쑀쟾옄移섎즺젣뒗 뼢썑 븘二 留롮 솚옄뱾쓽 궣쓣 諛붽퓭 넃쓣 쁺떊쟻 移섎즺젣媛 맆 寃”씠씪뒗 쟾留앹쓣 궡넃븯떎(Park, 2018).

씠 媛숈씠, 뿬윭 媛쒖쓽 쑀쟾옄移섎즺젣媛 엲떖븘 꽦怨듭쟻쑝濡 듅씤릺硫댁꽌, 꽭怨꾩쓽 쑀쟾옄移섎즺젣쓽 媛쒕컻怨 뿀媛 뿬嫄댁씠 留ㅼ슦 湲띿젙쟻쑝濡 蹂솕빐 媛怨 엳떎. 쑀쟾옄移섎즺젣 뿰援 媛쒕컻쓽 븵쓣 留됯퀬 엳뒗 뿬윭 媛吏 湲곗닠쟻, 젣룄쟻씤 궃愿룄 븯굹뵫 궗씪졇媛怨 엳떎. 떎뼇븳 쑀쟾옄移섎즺媛 媛쒕컻릺뼱꽌 씤瑜섏뿉寃 겙 怨좏넻쓣 二쇨퀬 엳뒗 븫씠굹 쑀쟾吏덊솚, 媛먯뿼吏덊솚, 꽦씤蹂묎낵 媛숈 뿬윭 媛吏 궃移섎퀝뿉꽌 깮紐낆쓣 援ы븯뒗 씗留앹씠 릺뼱 二쇨린瑜 湲곕븳떎.

ACKNOWLEDGMENTS

None.

CONFLICT OF INTEREST

No conflict of interests exists for any of the authors.

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