Haufinyane tjena, meriana e meraro ea kalafo ea lefutso e amohetsoe ho bapatsa, e leng: (1) Ka Phupu 21, 2022, PTC Therapeutics, Inc. (NASDAQ: PTCT) e phatlalalitse hore mofuta oa eona oa AAV gene therapy Upstaza™ o amohetsoe ke European Commission Ke pheko ea pele e rekisoang ea lefutso e kentsoeng bokong ka kotloloho (bona sengoloa se fetileng ho Generapy boko bo amohetsoe bakeng sa ho bapatsa).(2) Ka Phato 17, 2022, Tsamaiso ea Lijo le Lithethefatsi ea US (FDA) e amohetse Bluebird Bio's gene therapy Zynteglo (betibeglogene autotemcel, beti-cel) bakeng sa kalafo ea beta thalassemia.Ho amoheloa ha phekolo United States ha ho pelaelo hore ke "thuso lehloeng" bakeng sa Bluebird Bio, e leng mathateng a lichelete.(3) Ka Phato 24, 2022, BioMarin Pharmaceutical (BioMarin) e phatlalalitse hore Khomishene ea Europe e amohetse papatso e nang le maemo ea ROCTAVIAN™ (valoctocogene roxaparvovec), pheko ea lefutso bakeng sa hemophilia A, bakeng sa kalafo ea bakuli ba se nang nalane ea FVIII factor inhibitors le negative AAV5 antibodies ea AAV5 batho ba baholo ba hemophilia e fetileng! Phekolo ea lefutso e amohetsoeng bakeng sa ho bapatsa).Ho fihlela hajoale, litlhare tse 41 tsa kalafo ea lefutso li se li amohetsoe hore li bapatsoe lefatšeng ka bophara.

Gene ke karolo ea motheo ea liphatsa tsa lefutso e laolang mekhoa.Ntle le liphatsa tsa lefutso tsa likokoana-hloko tse ling, tse entsoeng ka RNA, liphatsa tsa lefutso tsa lintho tse ngata li entsoe ka DNA.Bongata ba mafu a lintho tse phelang bo bakoa ke tšebelisano lipakeng tsa liphatsa tsa lefutso le tikoloho, 'me mafu a mangata a ka phekoleha kapa a fokotsoa ha e le hantle ka phekolo ea lefutso.Phekolo ea liphatsa tsa lefutso e nkuoa e le phetoho lefapheng la bongaka le pharmacy.Lithethefatsi tse pharalletseng tsa liphatsa tsa lefutso li kenyelletsa lithethefatsi tse thehiloeng ho DNA-modified DNA (tse kang li-viral vector-based in vivo gene therapy drugs, in vitro gene therapy drugs, naked plasmid drugs, joalo-joalo) le lithethefatsi tsa RNA (tse kang antisense oligonucleotide drugs, siRNA drugs, le mRNA gene therapy, joalo-joalo);Litlhare tse hlalosoang ka mokhoa o patisaneng haholo tsa kalafo ea Gene li kenyelletsa lithethefatsi tsa plasmid DNA, litlhare tsa kalafo ea lefutso tse thehiloeng ho li-vector tsa vaerase, meriana ea kalafo ea lefutso e thehiloeng ho li-vector tsa baktheria, litsamaiso tsa ho hlophisa liphatsa tsa lefutso le litlhare tsa kalafo ea lisele tse fetotsoeng ka liphatsa tsa lefutso.Ka mor'a lilemo tsa tsoelo-pele e bohloko, meriana ea phekolo ea lefutso e fihletse liphello tse susumetsang tsa kliniki.(ntle le liente tsa DNA le liente tsa mRNA), meriana e 41 ea phekolo ea lefutso e amohetsoe hore e bapatsoe lefatšeng ka bophara.Ka ho hlahisoa ha lihlahisoa le nts'etsopele e potlakileng ea thekenoloji ea phekolo ea lefutso, phekolo ea lefutso e haufi le ho tlisa nako ea tsoelo-pele e potlakileng.

Sehlopha sa phekolo ea lefutso (Mohloli oa setšoantšo: Biological Jingwei)

Sengoliloeng sena se thathamisa liphekolo tse 41 tsa lefutso tse amohetsoeng bakeng sa ho bapatsa (ho sa kenyeletsoe liente tsa DNA le liente tsa mRNA).

1. Kalafo ea liphatsa tsa lefutso tsa in vitro

(1) Strimvelis

Khampani: E thehiloe ke GlaxoSmithKline (GSK).

Nako ea ho rekisoa: E amohetsoe ke European Union ka May 2016.

Lipontšo: Bakeng sa phekolo ea matla a kopantsoeng a immunodeficiency (SCID).

Litlhaloso: Mokhoa o akaretsang oa phekolo ena ke ho qala ka ho fumana lisele tsa mokuli tsa hematopoietic stem, ho li atolosa le ho li hlahisa ka har'a vitro, ebe o sebelisa retrovirus ho hlahisa kopi ea liphatsa tsa lefutso tsa ADA (adenosine deaminase) tse sebetsang ka har'a lisele tsa bona tsa hematopoietic stem, 'me qetellong li fetise lisele tsa stem tse fetotsoeng.Lisele tsa Hematopoietic stem li kenngoa hape 'meleng.Liphetho tsa bongaka li bonts'itse hore sekhahla sa ho phela sa lilemo tse 3 sa bakuli ba ADA-SCID ba phekoloang ka Strimvelis e bile 100%.

(2) Zalmoxis

Khampani: E hlahisitsoe ke MolMed, Italy.

Nako ea ho rekisa: E fumane tumello ea ho bapatsa e nang le maemo a EU ka 2016.

Lipontšo: E sebelisoa bakeng sa phekolo ea adjuvant ea tsamaiso ea 'mele ea ho itšireletsa mafung ea bakuli ka mor'a ho fetisetsa lisele tsa stem cell.

Maikutlo: Zalmoxis ke allogeneic T cell suicide gene immunotherapy e fetotsoeng ke vector ea retroviral.Liphatsa tsa lefutso tsa ho ipolaea tsa 1NGFR le HSV-TK Mut2 li lumella batho ho sebelisa ganciclovir ka nako leha e le efe ho bolaea lisele tsa T tse bakang likarabo tse mpe tsa 'mele oa ho itšireletsa mafung, ho thibela ho senyeha ho eketsehileng ha GVHD e ka' nang ea etsahala, le ho tsosolosa ts'ebetso ea 'mele ea ho itšireletsa mafung ho bakuli ba nang le HSCT ea haploidentical ka mor'a ho buuoa Escort.

(3) Invossa-K

Khampani: E thehiloe ke khamphani ea TissueGene (KolonTissueGene).

Nako ea ho rekisoa: E amohetsoe ho ngolisoa Korea Boroa ka Phupu 2017.

Lipontšo: Bakeng sa phekolo ea ramatiki ea mangole e senyehang.

Maikutlo: Invossa-K ke allogeneic cell gene therapy e kenyelletsang li-chondrocyte tsa batho.Lisele tsa allogeneic li na le liphatsa tsa lefutso tse fetotsoeng ka hare ho vitro, 'me lisele tse fetotsoeng li ka hlalosa le ho boloka phetoho ea kholo ea β1 (TGF-β1) ka mor'a ente ea intra-articular.β1), ka hona ho ntlafatsa matšoao a osteoarthritis.Liphetho tsa bongaka li bontša hore Invossa-K e ka ntlafatsa haholo ramatiki ea lengole.Laesense e ile ea hlakoloa ke molaoli oa lithethefatsi oa Korea Boroa ka 2019 hobane moetsi o ile a ngola ka mokhoa o fosahetseng metsoako e sebelisitsoeng.

(4) Zynteglo

Khampani: E thehiloe ke k'hamphani ea American bluebird bio (bluebird bio).

Nako ea ho rekisoa: E amohetsoe ke European Union ka 2019, mme e amohetsoe ke FDA ka Phato 2022.

Lipontšo: Bakeng sa phekolo ea β-thalassemia e itšetlehileng ka tšelo ea mali.

Maikutlo: Zynteglo ke lentiviral in vitro gene therapy, e sebelisang lentiviral vector ho hlahisa kopi e sebetsang ea gene e tloaelehileng ea β-globin (βA-T87Q-globin gene) liseleng tsa methapo ea mali e tlosoa ho bakuli., ebe o kenya lisele tsena tsa stem tsa autologous hematopoietic tse fetotsoeng ka liphatsa tsa lefutso ho khutlela ho mokuli.Hang ha mokuli a e-na le mofuta o tloaelehileng oa βA-T87Q-globin, a ka hlahisa protheine e tloaelehileng ea HbAT87Q, e ka fokotsang kapa ea felisa tlhokahalo ea tšelo ea mali ka katleho.Ke phekolo ea nako e le 'ngoe e etselitsoeng ho khutlisa tšelo ea mali ea bophelo bohle le meriana ea bophelo bohle bakeng sa bakuli ba lilemo tse 12 ho ea holimo.

(5) Skysona

Khampani: E thehiloe ke k'hamphani ea American bluebird bio (bluebird bio).

Nako ea ho mmaraka: E amohetsoe ke EU bakeng sa ho bapatsa ka Phupu 2021.

Lipontšo: Bakeng sa phekolo ea pele ea cerebral adrenoleukodystrophy (CALD).

Maikutlo: Kalafo ea liphatsa tsa lefutso ea Skysona ke eona feela phekolo ea nako e le 'ngoe ea lefutso e amohetsoeng bakeng sa phekolo ea cerebral adrenoleukodystrophy (CALD) ea pele.Skysona (elivaldogene autotemcel, Lenti-D) ke lentiviral in vitro gene therapy ea lenti-D.Mokhoa o akaretsang oa phekolo ke o latelang: lisele tsa stem tsa autologous hematopoietic li ntšoa ho mokuli, li fetotsoe ka in vitro ke lentivirus e jereng lefutso la ABCD1 la motho, ebe li khutlisetsoa ho mokuli.Bakeng sa kalafo ea bakuli ba ka tlase ho lilemo tse 18 ka phetoho ea liphatsa tsa lefutso tsa ABCD1 le CALD.

(6) Kymria

Khampani: E thehiloe ke Novartis.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Phato 2017.

Lipontšo: Kalafo ea precursor B-cell acute lymphoblastic leukemia (ALL) le DLBCL e khutletseng hape le refractory.

Maikutlo: Kymriah ke sethethefatsi sa lentiviral in vitro gene therapy, e leng phekolo ea pele e amohetsoeng lefatšeng ka bophara ea CAR-T, e shebaneng le CD19 le ho sebelisa co-stimulatory factor 4-1BB.Theko ke $475,000 US le $313,000 Japane.

(7) Yescarta

Khampani: E Thehiloe ke Kite Pharma, e leng lekala la Gileade.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Mphalane 2017.

Lipontšo: Bakeng sa phekolo ea ho khutlela morao kapa ho hanyetsa B-cell lymphoma e kholo.

Maikutlo: Yescarta ke phekolo ea liphatsa tsa lefutso tsa retroviral in vitro.Ke phekolo ea bobeli ea CAR-T e amohelehang lefatšeng.E shebane le CD19 mme e sebelisa costimulatory factor ea CD28.Litheko tsa US ke $373,000.

(8) Tecartus

Khampani: E Thehiloe ke Gileade (GILD).

Nako ea ho rekisoa: E amohetsoe ke FDA ka Phupu 2020.

Lipontšo: Bakeng sa ho khutlela morao kapa ho hanyetsa mantle cell lymphoma.

Maikutlo: Tecartus ke phekolo ea sele ea CAR-T e ikemetseng e shebileng CD19, 'me ke phekolo ea boraro ea CAR-T e amohetsoeng bakeng sa ho bapatsa lefatšeng.

(9) Breyanzi

Khampani: E thehiloe ke Bristol-Myers Squibb (BMS).

Nako ea ho rekisa: E amohetsoe ke FDA ka Hlakola 2021.

Lipontšo: Ho khutlela morao kapa ho hanyetsa (R / R) e kholo ea B-cell lymphoma (LBCL).

Maikutlo: Breyanzi ke in vitro gene therapy e thehiloeng ho lentivirus, 'me phekolo ea bone ea CAR-T e amohetsoeng bakeng sa ho bapatsa lefatšeng ka bophara, e lebisitsoe ho CD19.Kamohelo ea Breyanzi ke mohato oa bohlokoahali ho Bristol-Myers Squibb lebaleng la immunotherapy ea cellular, eo Bristol-Myers e e fumaneng ha e fumana Celgene ka $74 bilione ka 2019.

(10) Abecma

Khampani: E thehiloe ke Bristol-Myers Squibb (BMS) le bio bluebird.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Hlakubele 2021.

Matšoao: Ho khutlela morao kapa ho hanyetsa multiple myeloma.

Maikutlo: Abecma ke lentivirus-based in vitro gene therapy, kalafo ea pele ea lefats'e ea CAR-T e shebileng BCMA, le kalafo ea bohlano ea CAR-T e amohetsoeng ke FDA.Molao-motheo oa lithethefatsi ke ho hlahisa chimeric BCMA receptor ho lisele tsa T tsa mokuli tsa autologous ka lentivirus-mediated genetic modification in vitro.Pele ho tšeloa lithethefatsi tsa liphatsa tsa lefutso, mokuli o ile a fumana metsoako e 'meli ea cyclophosphamide le fludarabine bakeng sa phekolo ea pele.Kalafo ea ho tlosa lisele tsa T tse sa fetoloang ho mokuli, ebe o kenya lisele tsa T tse fetotsoeng hape 'meleng oa mokuli ho batla le ho bolaea lisele tsa mofetše tse hlahisang BCMA.

(11) Libmeldy

Khampani: E Thehiloe ke Orchard Therapeutics.

Nako ea ho rekisoa: E amohetsoe ke European Union bakeng sa ho ngolisoa ka December 2020.

Lipontšo: Bakeng sa phekolo ea metachromatic leukodystrophy (MLD).

Maikutlo: Libmeldy ke phekolo ea liphatsa tsa lefutso e thehiloeng ho lentiviral in vitro gene phetoho ea lisele tsa autologous CD34+.Lintlha tsa bongaka li bonts'a hore infusion e le 'ngoe ea methapo ea Libmeldy e sebetsa hantle ho fetoleng mokhoa oa pele oa ho qala MLD le ho senyeha ho matla ha motlakase le kelello ho bakuli ba sa alafshoang ba lilemo tse tšoanang.

(12) Benoda

Khampani: E thehiloe ke WuXi Junuo.

Nako ea ho rekisoa: E amohetsoe ka molao ke NMPA ka Loetse 2021.

Lipontšo: Kalafo ea ho khutlela morao kapa ho hanyetsa B-cell lymphoma e kholo (r / r LBCL) ho bakuli ba baholo ka mor'a phekolo ea bobeli kapa ho feta ea tsamaiso.

Maikutlo: Benoda ke phekolo ea lefutso ea anti-CD19 CAR-T, hape ke sehlahisoa sa mantlha sa WuXi Junuo.Ke sehlahisoa sa bobeli sa CAR-T se amohetsoeng Chaena, ntle le B-cell lymphoma e kholo e khutletseng hape.Ntle le moo, WuXi Junuo e boetse e rera ho nts'etsapele ente ea Ruiki Orenza bakeng sa kalafo ea matšoao a mang a fapaneng, ho kenyelletsa follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) , ea bobeli e hasanya B-cell lymphoma (DLBCL) le acute lymphoblastic leukemia (ALL).

(13) CARVYKTI

Khampani: Sehlahisoa sa pele se amohelehang sa Legend Bio.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Hlakola 2022.

Lipontšo: Kalafo ea ho khutlela morao kapa ho hanyetsa multiple myeloma (R / R MM).

Maikutlo: CARVYKTI (ciltacabtagene autoleucel, eo ho thoeng ke Cilta-cel) ke CAR-T cell immune gene therapy e nang le li-antibodies tse peli tsa domain tse lebisang B cell maturation antigen (BCMA).Lintlha li bontša hore CARVYKTI e bontšitse tekanyo ea kakaretso ea karabelo e fihlang ho 98% ho bakuli ba nang le myeloma ea ho khutlela morao kapa ea refractory ba neng ba fumane litlhare tse 'nè kapa ho feta pele, ho akarelletsa le proteasome inhibitors, immunomodulators le anti-CD38 monoclonal antibodies.

2. Kalafo ea liphatsa tsa lefutso ea in vivo e thehiloeng ho likokoana-hloko tsa kokoana-hloko

(1) Gendicine/tsalwa labobedi

Khampani: E thehiloe ke Khamphani ea Shenzhen Saibainuo.

Nako ea ho rekisoa: E amohetsoe ho ngolisoa Chaena ka 2003.

Lipontšo: Bakeng sa phekolo ea squamous cell carcinoma ea hlooho le molala.

Maikutlo: Recombinant human p53 adenovirus injection Gendicine/Jinshengsheng ke sethethefatsi sa adenovirus vector gene therapy se nang le litokelo tse ikemetseng tsa thepa ea mahlale tsa Khamphani ea Shenzhen Saibainuo.Lithethefatsi li entsoe ka liphatsa tsa lefutso tse tloaelehileng tsa "tumor suppressor" tsa p53 le ho feto-fetoha ka mokhoa o entsoeng ka mokhoa o entsoeng ka mokhoa o ts'oanang oa ho ikatisa-ho haella Motho adenovirus mofuta oa 5 o entsoe ka mofuta oa motho oa adenovirus oa 5. Ea pele ke mohaho o ka sehloohong oa lithethefatsi ho sebelisa phello e khahlanong le hlahala, 'me e qetellang e sebetsa haholo-holo e le mojari.Adenovirus vector e jara mofuta oa kalafo p53 ka seleng e shebiloeng, 'me e hlahisa mofuta oa tumor suppressor p53 ka seleng e shebiloeng.Sehlahisoa se ka laola mefuta e fapaneng ea liphatsa tsa lefutso tse khahlanong le mofets'e le ho theola mesebetsi ea li-oncogenes tse fapaneng, ka hona sa ntlafatsa phello ea anti-tumor ea 'mele le ho fihlela sepheo sa ho bolaea lihlahala.

(2) Rigvir

Khampani: E thehiloe ke k'hamphani ea Latvia ea Latima.

Nako ea ho rekisoa: E amohetsoe Latvia ka 2004.

Lipontšo: Bakeng sa phekolo ea melanoma.

Maikutlo: Rigvir ke phekolo ea liphatsa tsa lefutso e thehiloeng ho gene-modified ECHO-7 enterovirus vector, e 'nileng ea sebelisoa Latvia, Estonia, Poland, Armenia, Belarus le libakeng tse ling,' me e ntse e ngolisoa le EMA ea European Union..Linyeoe tsa bongaka lilemong tse leshome tse fetileng li pakile hore vaerase ea Rigvir oncolytic e bolokehile ebile e sebetsa, 'me e ka ntlafatsa sekhahla sa ho phela ha bakuli ba melanoma ka makhetlo a 4-6.Ntle le moo, kalafo e boetse e loketse mefuta e meng ea mofetše, ho kenyelletsa mofets'e oa colorectal, mofets'e oa manyeme, mofets'e oa senya.kankere, kankere ea liphio, kankere ea senya, kankere ea matšoafo, kankere ea popelo, lymphosarcoma, joalo-joalo.

(3) Oncorine/Ankerui

Khampani: E Thehiloe ke Shanghai Sunway Biotechnology Co., Ltd.

Nako ea ho rekisoa: E amohetsoe ho ngolisoa Chaena ka 2005.

Matšoao: Phekolo ea lihlahala tsa hlooho le molala, mofetše oa sebete, mofetše oa manyeme, mofetše oa popelo le mefuta e meng ea mofetše.

Maikutlo: Oncorine ke sehlahisoa sa kalafo sa oncolytic virus gene e sebelisang adenovirus joalo ka vector.The oncolytic adenovirus e fumanoeng e ka ikatisetsa ka ho khetheha lihlahala tse haellang kapa tse sa tloaelehang tsa p53, tse bakang tumor cell lysis, kahoo li bolaea lisele tsa tumor.ntle le ho senya lisele tse tloaelehileng.Liphetho tsa bongaka li bonts'a hore Anke Rui o na le polokeho e ntle le katleho bakeng sa mefuta e fapaneng ea lihlahala tse kotsi.

(4) Glybera

Khampani: E thehiloe ke UniQure.

Nako ea ho rekisoa: E amohetsoe Europe ka 2012.

Lipontšo: Phekolo ea khaello ea lipoprotein lipase (LPLD) e nang le liketsahalo tse matla kapa tse iphetang tsa pancreatitis ho sa tsotellehe lijo tse nang le mafura a mangata.

Maikutlo: Glybera (alipogene tiparvovec) ke moriana oa phekolo ea lefutso o thehiloeng ho AAV joalo ka vector.Phekolo ena e sebelisa AAV e le vector ho fetisetsa liphatsa tsa lefutso tsa LPL ka lisele tsa mesifa, e le hore lisele tse tsamaisanang li ka hlahisa palo e itseng ea lipoprotein lipase, E phetha karolo ea ho fokotsa maloetse, 'me phekolo ena e sebetsa nako e telele ka mor'a tsamaiso e le' ngoe (phello e ka tšoarella lilemo tse ngata).Setlhare sena se ile sa hlakoloa ka selemo sa 2017, 'me mabaka a ho hlakoloa ha sona a ka amana le lintlha tse peli: litheko tse phahameng haholo le tlhoko e fokolang ea mmaraka.Karolelano ea litšenyehelo tsa phekolo e le 'ngoe ea moriana e ka holimo ho liranta tse limilione tse 1 tsa US, 'me ke mokuli a le mong feela ea e rekileng le ho e sebelisa ho fihlela joale.Leha k'hamphani ea inshorense ea bongaka e ile ea e khutlisa ka lidolara tse 900,000 tsa US, e boetse ke moroalo o moholo ho k'hamphani ea inshorense.Ho phaella moo, pontšo bakeng sa lithethefatsi ke ntho e sa tloaelehang haholo, ka sekhahla sa liketsahalo tse ka bang 1 ho limilione tse 1 le tekanyo e phahameng ea ho se tsebe hantle.

(5) Imlygic

Khampani: E thehiloe ke Amgen.

Nako ea ho rekisoa: Ka 2015, e ile ea amoheloa bakeng sa ho ngolisoa United States le European Union.

Lipontšo: Kalafo ea melanoma e ke keng ea tlosoa ka ho feletseng ka ho buuoa.

Maikutlo: Imlygic ke liphatsa tsa lefutso tse fetotsoeng (ho hlakola likaroloana tsa liphatsa tsa lefutso tsa ICP34.5 le ICP47, le ho kenya motho granulocyte-macrophage colony-stimulating factor GM-CSF gene ka har'a kokoana-hloko) attenuated herpes simplex virus type 1 (HSV-1) oncolytic virus, the first FDA-approve virus therapy.Mokhoa oa tsamaiso ke ente ea intralesional.Ente e tobileng ka har'a melanoma e ka baka ho phatloha ha lisele tsa hlahala le ho lokolla li-antigen tse nkiloeng ho hlahala le GM-CSF ho khothaletsa likarabo tsa 'mele oa ho itšireletsa mafung.

(6) Luxturna

Khampani: E thehiloe ke Spark Therapeutics, e leng setsi sa Roche.

Nako ea ho rekisoa: E amohetsoe ke FDA ka selemo sa 2017, ebe e amoheloa bakeng sa ho bapatsa Europe ka 2018.

Lipontšo: Bakeng sa phekolo ea bana le batho ba baholo ba nang le tahlehelo ea pono ka lebaka la ho fetoha ha likopi tse peli tsa lefutso la RPE65 empa ka lipalo tse lekaneng tsa lisele tse sebetsang tsa retinal.

Maikutlo: Luxturna ke phekolo ea lefutso e thehiloeng ho AAV e tsamaisoang ka ente ea subretinal.Phekolo ea liphatsa tsa lefutso e sebelisa AAV2 e le sesebelisoa ho hlahisa kopi e sebetsang ea mofuta o tloaelehileng oa RPE65 liseleng tsa retina tsa mokuli, e le hore lisele tse tsamaisanang le tsona li hlahise protheine e tloaelehileng ea RPE65 ho lefella sekoli sa protheine ea RPE65 ea mokuli, kahoo e ntlafatsa pono ea mokuli.

(7) Zolgensma

Khamphani: E thehiloe ke AveXis, e leng setsi sa Novartis.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Mots'eanong 2019.

Lipontšo: Kalafo ea mokokotlo oa mokokotlo oa mokokotlo (Spinal Muscular Atrophy, SMA) bakuli ba ka tlase ho lilemo tse peli.

Maikutlo: Zolgensma ke phekolo ea lefutso e thehiloeng ho vector ea AAV.Setlhare sena ke morero oa nako e le 'ngoe feela oa kalafo bakeng sa mokokotlo oa mokokotlo oa mokokotlo o lumelletsoeng ho rekisoa lefatšeng.leqephe, ke tsoelo-pele ea bohlokoahali.Pheko ena ea liphatsa tsa lefutso e sebelisa vector ea scAAV9 ho hlahisa mofuta o tloaelehileng oa SMN1 ho bakuli ka ho tšeloa ka methapo, ho hlahisa protheine e tloaelehileng ea SMN1, ka hona ho ntlafatsa ts'ebetso ea lisele tse amehileng joalo ka li-motor neurons.Ka lehlakoreng le leng, lithethefatsi tsa SMA Spinraza le Evrysdi li hloka ho noa khafetsa ka nako e telele, 'me Spinraza e tsamaisoa e le ente ea mokokotlo ka mor'a likhoeli tse ling le tse ling tse' nè, le Evrysdi, lithethefatsi tsa letsatsi le letsatsi tsa molomo.

(8) Delytact

Khampani: E Thehiloe ke Daiichi Sankyo Company Limited (TYO: 4568).

Nako ea ho mmaraka: Tumello e nang le maemo ho tsoa Lefapheng la Bophelo bo Botle la Japane, Basebetsi le Boiketlo (MHLW) ka Phuptjane 2021.

Lipontšo: Bakeng sa phekolo ea malignant glioma.

Maikutlo: Delytact ke sehlahisoa sa bone sa oncolytic virus gene therapy se amohetsoeng lefatšeng ka bophara ebile ke sehlahisoa sa pele sa vaerase sa oncolytic se amohetsoeng bakeng sa kalafo ea malignant glioma.Delytact ke kokoana-hloko e entsoeng ka liphatsa tsa lefutso ea herpes simplex virus mofuta oa 1 (HSV-1) oncolytic virus e entsoeng ke Dr. Todo le basebetsi-'moho.Delytact e hlahisa phetoho e eketsehileng ea ho hlakoloa ho genome ea G207 ea HSV-1 ea moloko oa bobeli, e ntlafatsa ho ikatisa ha eona ka har'a lisele tsa mofetše le ho kenngoa ha likarabo tsa ho itšireletsa mafung, ha li ntse li boloka boemo bo phahameng ba tšireletso.Delytact ke moloko oa boraro oa oncolytic HSV-1 hajoale tlhahlobong ea bongaka.Tumello ea Delytact naheng ea Japane e thehiloe tekong ea bongaka ea Mokhahlelo oa 2 oa letsoho le le leng.Ho bakuli ba nang le glioblastoma e tloaelehileng, Delytact e ile ea kopana le qetello ea pele ea ho phela ha selemo se le seng, 'me liphello li bontšitse hore Delytact e sebetsa hantle ho feta G207.Katiso e matla le ts'ebetso e phahameng ea antitumor.Sena se sebetsa mefuteng e tiileng ea hlahala ho kenyelletsa sefuba, prostate, schwannoma, nasopharyngeal, hepatocellular, colorectal, malignant peripheral nerve sheath tumors le mofets'e oa qoqotho.

(9) Upstaza

Khampani: E Thehiloe ke PTC Therapeutics, Inc. (NASDAQ: PTCT).

Nako ea ho mmaraka: E amohetsoe ke EU ka Phupu 2022.

Pontšo: Bakeng sa khaello e nkhang hamonate ea L-amino acid decarboxylase (AADC), e amohetsoeng bakeng sa kalafo ea bakuli ba likhoeli tse 18 ho ea holimo.

Maikutlo: Upstaza™ (eladocagene exuparvovec) ke in vivo gene therapy e sebelisang adeno-associated virus type 2 (AAV2) joalo ka vector.Mokuli o kula ka lebaka la phetoho ea liphatsa tsa lefutso tse kenyang enzyme ea AADC.AAV2 e na le mofuta o phetseng hantle o kenyang enzyme ea AADC.Phello ea phekolo e finyelloa ka mokhoa oa matšeliso a lefutso.Ka khopolo, tekanyo e le 'ngoe e sebetsa ka nako e telele.Ke pheko ea pele ea liphatsa tsa lefutso e rekisoang e kentsoeng bokong ka kotloloho.Tumello ea ho bapatsa e sebetsa ho linaha tsohle tse 27 tseo e leng litho tsa EU, hammoho le Iceland, Norway le Liechtenstein.

(9) Roctavian

Khampani: E thehiloe ke BioMarin Pharmaceutical (BioMarin).

Nako ea ho rekisoa: E amohetsoe ke EU ka Phato 2022.

Lipontšo: Bakeng sa phekolo ea bakuli ba baholo ba nang le hemophilia e matla A ntle le histori ea FVIII factor inhibition le AAV5 antibody negative.

Maikutlo: Roctavian (valoctocogene roxaparvovec) e sebelisa AAV5 joalo ka vector 'me e sebelisa HLP e ikhethileng ka sebete sa motho ho tsamaisa polelo ea human coagulation factor eight (FVIII) mme sebaka sa B se hlakotsoe.Qeto ea Khomishene ea Europe ea ho fana ka tumello ea ho bapatsa valoctocogene roxaparvovec e ipapisitse le lintlha tse akaretsang tsa lenaneo la ntlafatso ea bongaka ba moriana.Har'a bona, teko ea kliniki ea mohato oa III GENEr8-1 e bontšitse hore ha e bapisoa le lintlha tsa selemo pele ho ngolisoa, ka mor'a hore ho be le infusion e le 'ngoe ea valoctocogene roxaparvovec, Barupeluoa ba ne ba e-na le tekanyo e tlaase haholo ea selemo ea ho tsoa mali (ABR), tšebeliso e fokolang khafetsa ea litokisetso tsa protheine ea factor VIII (F8), kapa keketseho e kholo ea mosebetsi oa F8 maling a' mele.Kamora libeke tse 4 tsa kalafo, tšebeliso ea selemo le selemo ea F8 ea baithuti le ABR e hlokang kalafo e fokotsoe ka 99% le 84%, ka ho latellana, phapang ea bohlokoa ea lipalo (p<0.001).Boemo ba ts'ireletso bo ne bo le monate, ho se na batho ba nang le F8 factor inhibition, malignancy, kapa thrombotic side effects, 'me ha ho liketsahalo tse mpe tse amanang le phekolo (SAEs) tse tlalehiloeng.

3. Lithethefatsi tse nyenyane tsa nucleic acid

(1) Vitravene

Khampani: E entsoe ka kopanelo ke Ionis Pharma (eo pele e neng e le Isis Pharma) le Novartis.

Nako ea ho rekisoa: E amohetsoe ke FDA le EU EMA ka 1998 le 1999.

Lipontšo: Bakeng sa phekolo ea cytomegalovirus retinitis ho bakuli ba nang le HIV.

Litlhaloso: Vitravene ke lithethefatsi tsa antisense oligonucleotide le lithethefatsi tsa pele tsa oligonucleotide tse amohelehang bakeng sa ho rekisoa lefatšeng.Qalong ea 'maraka, tlhokahalo ea' maraka ea lithethefatsi tse khahlanong le cytomegalovirus e ne e potlakile haholo;joale ka lebaka la nts'etsopele ea phekolo e sebetsang haholo ea li-antiretroviral, palo ea linyeoe tsa cytomegalovirus e ile ea theoha haholo.Ka lebaka la tlhokahalo e tlase ea 'maraka, sethethefatsi se ile sa lokolloa ka 2002 le 2006 Ho tlohela linaheng tsa EU le US.

(2) Macugen

Khampani: E thehiloe ke Pfizer le Eyetech.

Nako ea ho rekisoa: E amohetsoe ho ngolisoa United States ka 2004.

Lipontšo: Bakeng sa phekolo ea ho senyeha ha macular ho amanang le lilemo tsa neovascular.

Mantsoe: Macugen ke pegylated modified oligonucleotide drug e ka lebisang le ho tlama ho vascular endothelial growth factor (VEGF165 isoform), 'me e tsamaisoa ke ente ea intravitreal.

(3) Defitelio

Khampani: E ntlafalitsoe ke Jazz.

Nako ea ho rekisoa: E amohetsoe ke European Union ka 2013, mme e amohetsoe ke FDA ka Hlakubele 2016.

Lipontšo: Bakeng sa phekolo ea lefu la hepatic venule occlusive le amanang le ho se sebetse ha renal kapa pulmonary ka mor'a ho fetisoa ha lisele tsa lisele tsa hematopoietic.

Maikutlo: Defitelio ke lithethefatsi tsa oligonucleotide, motsoako oa oligonucleotides le thepa ea plasmin.E ile ea tlosoa ka 2009 ka mabaka a khoebo.

(4) Kynamro

Khampani: E thehiloe ke Ionis Pharma le Kastle.

Nako ea ho rekisoa: E amohetsoe United States e le sethethefatsi sa likhutsana ka 2013.

Lipontšo: Bakeng sa phekolo ea adjuvant ea homozygous family hypercholesterolemia.

Maikutlo: Kynamro ke sethethefatsi sa oligonucleotide sa antisense, oligonucleotide ea antisense e shebileng motho apo B-100 mRNA.Kynamro e tsamaisoa e le 200 mg subcutaneously hang ka beke.

(5) Spinraza

Khampani: E thehiloe ke Ionis Pharmaceuticals.

Nako ea ho rekisoa: E amohetsoe ke FDA ka December 2016.

Lipontšo: Bakeng sa phekolo ea spinal muscular atrophy (SMA).

Maikutlo: Spinraza (nusinersen) ke sethethefatsi sa oligonucleotide sa antisense.Spinraza e ka fetola RNA splicing ea SMN2 gene ka ho tlama sebakeng sa splicing sa SMN2 exon 7, kahoo e eketsa tlhahiso ea protheine ea SMN e sebetsang ka botlalo.Ka Phato 2016, BIOGEN Corporation e sebelisitse khetho ea eona ea ho fumana litokelo tsa lefats'e tsa Spinraza.Spinraza e qalile teko ea eona ea pele ea kliniki ho batho ka 2011. Ka lilemo tse 5 feela, e ile ea amoheloa ke FDA ka 2016, e bontšang hore FDA e ananela ka botlalo ho sebetsa ha eona.Setlhare se ile sa amoheloa bakeng sa ho rekisoa Chaena ka April 2019. Nako eohle ea tumello ea Spinraza Chaena e ka tlase ho likhoeli tse 6.E se e le lilemo tse 2 le likhoeli tsa 2 ho tloha ha Spinraza e amoheloa ka lekhetlo la pele United States.Lefu le joalo la blockbuster kantle ho naha le sa tloaelehang sethethefatsi se secha se ka Lebelo la ho thathamisa China le se le ntse le potlakile haholo.Sena se boetse se bakoa ke "Tsebiso mabapi le Phatlalatso ea Lethathamo la Pele la Lithethefatsi tse Ncha tsa Maoatle tse Hlokehang ka Potlako bakeng sa Patlisiso ea Tleliniki" e fanoeng ke Setsi sa Tlhahlobo ea Lithethefatsi ka la 1 Pulungoana 2018, e kenyellelitsoeng sehlopheng sa pele sa lithethefatsi tse ncha tse 40 tsa kantle ho naha bakeng sa tlhahlobo e potlakileng, mme Spinraza e behiloe ho.

(6) Exoda 51

Khampani: E thehiloe ke AVI BioPharma (hamorao e ile ea rehoa Sarepta Therapeutics).

Nako ea ho rekisoa: E amohetsoe ke FDA ka Loetse 2016.

Lipontšo: Bakeng sa phekolo ea Duchenne muscular dystrophy (DMD) ka phetoho ea liphatsa tsa lefutso tsa DMD ka exon 51 skipping gene.

Tlhaloso: Exondys 51 ke sethethefatsi sa oligonucleotide sa antisense.Antisense oligonucleotide e ka tlama sebakeng sa exon 51 sa pre-mRNA ea lefutso la DMD, e leng se etsang hore ho thehoe mRNA e hōlileng.Excision, ka tsela eo e lokisa ka mokhoa o sa fellang foreimi ea ho bala ea mRNA, e thusa mokuli ho etsa mefuta e meng e sebetsang ea dystrophin e khutšoanyane ho feta protheine e tloaelehileng, kahoo e ntlafatsa matšoao a mokuli.

(7) Tegsedi

Khampani: E thehiloe ke Ionis Pharmaceuticals.

Nako ea ho rekisoa: E amohetsoe ke European Union bakeng sa ho bapatsa ka Phupu 2018.

Lipontšo: Bakeng sa phekolo ea hereditary transthyretin amyloidosis (hATTR).

Maikutlo: Tegsedi ke sethethefatsi sa oligonucleotide sa antisense se lebisang ho transthyretin mRNA.Ke sethethefatsi sa pele se amohetsoeng lefatšeng sa kalafo ea hATTR.Mokhoa oa tsamaiso ke subcutaneous injection.Sethethefatsi se fokotsa tlhahiso ea protheine ea ATTR ka ho lebisa mRNA ea transthyretin (ATTR), 'me e na le tekanyo e ntle ea kotsi ea melemo ea phekolo ea ATTR.Leha ho le joalo, boemo ba lefu kapa boteng ba lefu la pelo bo ne bo sa ameha.

(8) Onpattro

Khampani: E ntlafalitsoe ke Alnylam le Sanofi.

Nako ea ho rekisoa: E amohetsoe ho ngolisoa United States ka 2018.

Lipontšo: Bakeng sa phekolo ea hereditary transthyretin amyloidosis (hATTR).

Litlhaloso: Onpattro ke lithethefatsi tsa siRNA tse lebisang ho transthyretin mRNA, e fokotsang tlhahiso ea protheine ea ATTR sebeteng le ho bokella li-amyloid deposits meleng ea peripheral ka ho lebisa mRNA ea transthyretin (ATTR)., ka hona ho ntlafatsa le ho imolla matšoao a lefu.

(9) Givlaari

Khampani: E Thehiloe ke Alnylam Corporation.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Pulungoana 2019.

Lipontšo: Bakeng sa phekolo ea acute hepatic porphyria (AHP) ho batho ba baholo.

Maikutlo: Givlaari ke sethethefatsi sa siRNA, sethethefatsi sa bobeli sa siRNA se lumelletsoeng ho rekisoa ka mor'a Onpattro.Setlhare se tsamaisoa ka tlas'a letlalo 'me se lebisa mRNA bakeng sa ho senyeha ha protheine ea ALAS1.Kalafo ea khoeli le khoeli ea Givlaari e ka fokotsa haholo 'me ka nako e telele boemo ba ALAS1 sebeteng, kahoo ea fokotsa maemo a neurotoxic ALA le PBG ho ea boemong bo tloaelehileng, kahoo ea Fokotsa matšoao a lefu la mokuli.Lintlha li bontšitse hore bakuli ba tšoaroang ka Givlaari ba ne ba e-na le phokotso ea 74% ea palo ea mafu a mafu ha a bapisoa le sehlopha sa placebo.

(10) Vyondys53

Khampani: E thehiloe ke Sarepta Therapeutics.

Nako ea ho rekisoa: E amohetsoe ke FDA ka December 2019.

Pontšo: Bakeng sa kalafo ea bakuli ba DMD ba nang le lefu la dystrophin exon 53 splice mutation.

Maikutlo: Vyondys 53 ke sethethefatsi sa oligonucleotide sa antisense.Sethethefatsi sa oligonucleotide se shebile mokhoa oa ho kopanya oa dystrophin mRNA precursor.Ka mokhoa o sa tobang oa dystrophin mRNA precursor, Exon 53 ea kantle e ne e arotsoe ka mokhoa o itseng, ke hore, ha e fumanehe ho mRNA e hōlileng, 'me e ne e etselitsoe ho hlahisa protheine ea dystrophin e fokolang empa e ntse e sebetsa, kahoo e ntlafatsa bokhoni ba boikoetliso ho bakuli.

(11) Waylivra

Khampani: E thehiloe ke Ionis Pharmaceuticals le setsi sa eona sa Akcea Therapeutics.

Nako ea ho rekisoa: E amohetsoe ke European Medicines Agency (EMA) ka Mots'eanong 2019.

Pontšo: E le phekolo ea tlatsetso ho lijo tse laoloang ho bakuli ba baholo ba nang le lefu la chylomicronemia syndrome (FCS).

Maikutlo: Waylivra ke sethethefatsi sa oligonucleotide sa antisense, e leng moriana oa pele o amohetsoeng bakeng sa kalafo ea FCS lefatšeng.

(12) Leqvio

Khampani: E thehiloe ke Novartis.

Nako ea ho rekisoa: E amohetsoe ke EU ka December 2020.

Lipontšo: Bakeng sa kalafo ea hypercholesterolemia ea batho ba baholo (heterozygous family and non-family) kapa dyslipidemia e tsoakiloeng.

Maikutlo: Leqvio ke sethethefatsi sa siRNA se shebileng PCSK9 mRNA.Ke phekolo ea pele lefatšeng ea ho theola k'holeseterole (LDL-C) siRNA.Mokhoa oa tsamaiso ke subcutaneous injection.Setlhare se sebetsa ka tšitiso ea RNA ho theola maemo a protheine ea PCSK9, e leng eona e theolang maemo a LDL-C.Lintlha tsa bongaka li bonts'a hore Leqvio e ka fokotsa LDL-C ka hoo e ka bang 50% ho bakuli bao maemo a bona a LDL-C a ke keng a theoleloa ho maemo a reretsoeng ho sa tsotellehe litekanyetso tse ngata tse mamelloang tsa li-statins.

(13) Ntlafatso

Khampani: E Thehiloe ke Alnylam Pharmaceuticals.

Nako ea ho rekisoa: E amohetsoe ke EU ka Pulungoana 2020.

Lipontšo: Bakeng sa phekolo ea mofuta oa mantlha oa hyperoxaluria 1 (PH1).

Maikutlo: Oxlumo ke moriana oa siRNA o lebisitseng hydroxy acid oxidase 1 (HAO1) ​​mRNA, e tsamaisoang ka tlas'a letlalo.Setlhare sena se entsoe ho sebelisoa theknoloji ea morao-rao e ntlafalitsoeng ea Alnylam ea ho tsitsisa ea lik'hemik'hale ESC-GalNAc, e nolofalletsang li-siRNA tse tsamaisoang ka mokhoa o sa tsitsang ka phehello le katleho e kholo.Moriana ona o lebisa tlhokomelo ho senyeha kapa ho thibela hydroxy acid oxidase 1 (HAO1) ​​mRNA, e fokotsa boemo ba glycolate oxidase sebeteng, ebe e sebelisa substrate e hlokahalang bakeng sa tlhahiso ea oxalate le ho fokotsa tlhahiso ea oxalate ho laola tsoelo-pele ea mafu le ho ntlafatsa matšoao a lefu ho bakuli.

(14) Viltepso

Khampani: E thehiloe ke NS Pharma, e leng setsi sa Nippon Shinyaku.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Phato 2020.

Lipontšo: Bakeng sa phekolo ea Duchenne muscular dystrophy (DMD) ka phetoho ea liphatsa tsa lefutso tsa DMD ka exon 53 skipping gene.

Maikutlo: Viltepso ke sethethefatsi sa phosphorodiamide morpholino oligonucleotide.Sethethefatsi sena sa oligonucleotide se ka tlama sebakeng sa exon 53 sa pre-mRNA ea lefutso la DMD, e leng se etsang hore ho thehoe mRNA e hōlileng tsebong.Exon e tlosoa ka mokhoa o itseng, kahoo e lokisa ka mokhoa o sa fellang foreimi ea ho bala ea mRNA, e thusa mokuli ho etsa mefuta e meng ea ts'ebetso ea dystrophin e khutšoanyane ho feta protheine e tloaelehileng, kahoo e ntlafatsa matšoao a mokuli.

(15) Amvuttra (vutrisiran)

Khampani: E Thehiloe ke Alnylam Pharmaceuticals.

Nako ea ho rekisoa: E amohetsoe ke FDA ka Phuptjane 2022.

Lipontšo: Bakeng sa phekolo ea lefutso la batho ba baholo ba transthyretin amyloidosis le polyneuropathy (hATTR-PN).

Maikutlo: Amvuttra (Vutrisiran) ke moriana oa siRNA o lebisitseng transthyretin (ATTR) mRNA, e tsamaisoang ka ente e ka tlas'a letlalo.Vutrisiran e entsoe ho ipapisitsoe le sethala sa Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc se nang le matla a eketsehileng le botsitso ba metabolic.Tumello ea phekolo e thehiloe boitsebisong ba likhoeli tsa 9 ho tloha thutong ea eona ea meriana ea Phase III (HELIOS-A), ka liphello tse akaretsang tse bontšang hore phekolo e ntlafalitse matšoao a hATTR-PN, ka bakuli ba fetang 50% ba khutlisetsa morao kapa ba emisa tsoelo-pele.

4. Lithethefatsi tse ling tsa phekolo ea lefutso

(1) Rexin-G

Khampani: E thehiloe ke Epeius Biotech.

Nako ea ho rekisoa: E amohetsoe ke Tsamaiso ea Lijo le Lithethefatsi ea Philippines (BFAD) ka 2005.

Lipontšo: Bakeng sa phekolo ea kankere e tsoetseng pele e hanyetsanang le chemotherapy.

Maikutlo: Rexin-G ke ente ea nanoparticle e tletseng liphatsa tsa lefutso.E hlahisa mofuta oa cyclin G1 o fetotsoeng ka har'a lisele tse shebiloeng ka vector ea retroviral ho bolaea ka ho khetheha lihlahala tse tiileng.Mokhoa oa tsamaiso ke intravenous infusion.E le moriana o lebisitsoeng ho hlahala o batlang ka mafolofolo le ho senya lisele tsa mofetše oa metastatic, o na le phello e itseng ho bakuli ba sa sebetseng khahlanong le lithethefatsi tse ling tsa mofetše, ho kenyeletsoa le biologics e lebisitsoeng.

(2) Neovasculgen

Khampani: E thehiloe ke Setsi sa Li-Stem cell.

Nako ea ho ngoloa: E amohetsoe hore e ngolisoe Russia ka la 7 Tšitoe, 2011, eaba e thathamisoa Ukraine ka 2013.

Lipontšo: Bakeng sa phekolo ea lefu la peripheral arterial, ho akarelletsa le ischemia e matla ea maoto.

Tlhaloso: Neovasculgen ke DNA plasmid-based gene therapy moo vascular endothelial growth factor (VEGF) 165 gene e entsoeng ka mokokotlo oa plasmid mme e kenngoa ho bakuli.

(3) Collategene

Khamphani: E thehiloe ke Univesithi ea Osaka le lifeme tsa capital capital.

Nako ea ho etsa lethathamo: E amohetsoe ke Lefapha la Bophelo bo Botle la Japane, Basebetsi le Boiketlo bakeng sa ho ngolisoa ka Phato 2019.

Lipontšo: Kalafo ea ischemia e matla e tlase.

Maikutlo: Collategene ke phekolo ea liphatsa tsa lefutso e thehiloeng ho plasmid, sethethefatsi sa pele sa tlhaho sa Japane sa kalafo se hlahisoang ke AnGes.Karolo e ka sehloohong ea lithethefatsi ena ke plasmid e hlobotseng e nang le tatellano ea liphatsa tsa lefutso tsa human hepatocyte growth factor (HGF).Haeba moriana o kenngoa ka har'a mesifa ea maoto a ka tlaase, HGF e hlalositsoeng e tla khothalletsa ho thehoa ha methapo e mecha ea mali ho pota-potile methapo ea mali e koetsoeng.Liteko tsa bongaka li netefalitse katleho ea eona ho ntlafatsa liso.

QETA