Majini ndiwo akakosha genetic units anodzora hunhu.Kunze kwemajini emamwe mavhairasi, ayo anoumbwa neRNA, majini ezvipenyu zvakawanda anoumbwa neDNA..Zvirwere zvakawanda zvezvipenyu zvinokonzerwa nekudyidzana pakati pemajini uye zvakatipoteredza.Gene therapy inogona kurapa kana kuderedza zvirwere zvakawanda.Gene therapy inoonekwa seshanduko mumunda wemishonga uye pharmacy.Gene therapy mishonga mupfungwa yakafara inosanganisira inobva paDNA-modified DNA drugs (senge in vivo gene therapy drugs based on viral vectors, in vitro gene therapy drugs, zvinodhaka zveplasmid zvisina kupfeka, nezvimwewo) nemishonga yeRNA (senge antisense oligonucleotide drugs, siRNA drugs, uye mRNA gene therapy, nezvimwewo);nhete yeGene therapy mishonga inonyanya kusanganisira plasmid DNA mishonga, gene therapy mishonga yakavakirwa pamavhairasi mavhairasi, gene therapy mishonga yakavakirwa pamabhakitiriya vectors, gene editing systems, uye cell therapy mishonga ye in vitro gene modification.Mushure memakore ekukura kunorwadza, gene therapy mishonga yakawana zvinokurudzira zvekiriniki.(Tisingaverenge majekiseni eDNA uye majekiseni emRNA) Parizvino, 45 gene therapy mishonga yakabvumidzwa kutengeswa munyika.Huwandu hwe9 gene marapirwo akatenderwa kushambadzira gore rino, kusanganisira 7 gene marapirwo akabvumidzwa kushambadzira kekutanga gore rino, anoti: CARVYKTI, Amvuttra, Upstaza, Roctavian, Hemgenix, Adstiladrin naEbvallo, (Cherechedza: Mamwe maviri akabvumidzwa muUnited States gore rino. FDA yekushambadzira muUnited States muna Nyamavhuvhu 2022, uye yakatenderwa kushambadzira neEuropean Union muna 2019;.) Nekuparurwa kweakawanda uye akawanda gene therapy zvigadzirwa uye kukurumidza kuvandudzwa kweiyo gene therapy tekinoroji, gene therapy yave kuda kuunza nguva yekukura nekukurumidza.

Kurongeka kwegene therapy (Mufananidzo sosi: Bio-Matrix)

Chinyorwa ichi chinonyora makumi mana neshanu ekurapa kwemajini (tisingasanganisi majekiseni eDNA uye majekiseni emRNA) ayo akatenderwa kushambadzira.

1. In vitro gene therapy

(1) Strimvelis

Kambani: Yakagadzirwa neGlaxoSmithKline (GSK).

Nguva yemusika: Yakatenderwa kushambadzira neEuropean Union muna Chivabvu 2016.

Zvinoratidza: Pakurapa kwakanyanya kusanganisa immunodeficiency (SCID).

Tsanangudzo: Iyo nzira yekurapa iyi ndeyekutanga kuwana murwere ega hematopoietic stem masero, kuwedzera uye tsika iwo in vitro, zvino shandisa retrovirus kuunza inoshanda ADA (adenosine deaminase) gene kopi muhematopoietic stem masero, uye pakupedzisira jekiseni akagadziridzwa Hematopoietic stem masero anodzoserwa zvakare mumuviri.Mibairo yemakiriniki inoratidza kuti makore matatu ekupona kwevarwere veADA-SCID vanorapwa neStrimvelis i100%.

(2) Zalmoxis

Kambani: Yakagadzirwa neItaly MolMed Kambani.

Nguva yemusika: Yakawana mvumo yekushambadzira kubva kuEuropean Union muna 2016.

Zvinoratidza: Inoshandiswa kune adjuvant kurapa kwea immune system yevarwere mushure meiyo hematopoietic stem cell transplantation.

Tsanangudzo: Zalmoxis is allogeneic T cell suicide gene immunotherapy yakagadziridzwa neretroviral vectors.Iyi nzira inoshandisa retroviral vectors kuti genetically modify allogeneic T masero, kuitira kuti masero eT akagadziridzwa aratidze 1NGFR uye HSV-TK Mut2 kuzviuraya majini anobvumira vanhu kushandisa ganciclovir (ganciclovir) zvinodhaka chero nguva kuuraya masero eT anokonzera kusagadzikana kwemaitiro ekudzivirira muviri, kudzivirira zvichibvira kuwedzera kuderera kwehutano hwehutachiona hweGVHS uye kupa GVHS reconstruction yeGVHD, reconstruction reconstruction yeGVHD.

(3) Invossa-K

Kambani: Yakagadzirwa neTissueGene (KolonTissueGene).

Nguva yemusika: Yakatenderwa kunyorwa muSouth Korea muna Chikunguru 2017.

Zviratidzo: Kurapa kwekuparara kwemabvi arthritis.

Mashoko: Invossa-K inonzi allogeneic cell gene therapy inosanganisira chondrocytes yevanhu.Masero anonzi allogeneic ane genetically modified in vitro, uye masero akashandurwa anogona kuratidza uye kuvhara kushandura kushandura kukura chinhu β1 (TGF-β1) mushure mejojo ​​ye intra-articular.β1), nokudaro achivandudza zviratidzo zveosteoarthritis.Migumisiro yemakiriniki inoratidza kuti Invossa-K inogona kuvandudza zvakanyanya arthritis yemabvi.Yakabviswa muna 2019 neKorea Chikafu neDrug Administration nekuti mugadziri wacho akadudza zvisizvo zvinoshandiswa.

(4) Zynteglo

Kambani: Yakatsvakwa uye yakagadziridzwa nebluebird bio.

Nguva yemusika: Yakatenderwa neEuropean Union yekushambadzira muna 2019, uye yakatenderwa neFDA kushambadzira muUnited States muna Nyamavhuvhu 2022.

Zvinoratidza: Zvekurapa kwekuisira ropa-inotsamira β-thalassemia.

Tsanangudzo: Zynteglo inonzi lentiviral in vitro gene therapy iyo inotanga kopi inoshanda yeanowanzo β-globin gene (βA-T87Q-globin gene) muhematopoietic stem masero anotorwa kubva kumurwere kuburikidza ne lentiviral vector, uye ozodzorerazve aya genetically modified autologous hematopoietic stem cells.Kana murwere angove neakajairika βA-T87Q-globin gene, anogona kugadzira yakajairika HbAT87Q protein, inogona kunyatso kudzikisa kana kubvisa kudiwa kwekuwedzerwa ropa.Inguva imwe chete yekurapa yakagadzirirwa kutsiva kuwedzerwa ropa kwehupenyu hwese uye mishonga yeupenyu hwese kune varwere vane makore gumi nemaviri zvichikwira.

(5) Skysona

Kambani: Yakatsvakwa uye yakagadziridzwa nebluebird bio.

Nguva yemusika: Yakatenderwa neEuropean Union kushambadzira muna Chikunguru 2021, uye yakatenderwa neFDA kushambadzira muUnited States munaGunyana 2022.

Zviratidzo: Pakurapa kwekutanga cerebral adrenoleukodystrophy (CALD).

Remarks: Skysona gene therapy ndiyo yega-nguva imwe chete gene therapy inotenderwa kurapwa kwekutanga-stage cerebral adrenoleukodystrophy (CALD).Skysona (elivaldogene autotemcel, Lenti-D) is hematopoietic stem cell lentiviral in vitro gene therapy Lenti-D.Maitiro akajairika ekurapa ndeaya anotevera: autologous hematopoietic stem masero anotorwa kubva kumurwere, anotapurwa uye anogadziriswa ne lentivirus inotakura yemunhu ABCD1 gene in vitro, uye yodzoserwa kumashure kumurwere.Inoshandiswa kurapa varwere vari pasi pemakore gumi nemasere, vakatakura ABCD1 gene mutations, uye CALD.

(6) Kymriah

COMPANY: Yakagadzirwa naNovartis.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Nyamavhuvhu 2017.

Zviratidzo: Kurapa kwe precursor B-cell acute lymphoblastic leukemia (ALL) uye yakadzoka zvakare uye inoramba DLBCL.

Mashoko: Kymriah mushonga welentiviral in vitro gene therapy, yekutanga CAR-T kurapa yakatenderwa kushambadzira munyika, yakanangana neCD19, uye kushandisa 4-1BB co-stimulatory factor.Mutengo weUS $475,000 muUS uye $313,000 muJapan.

(7) Yescarta

Kambani: Yakagadzirwa naKite Pharma, inotsigira yeGiriyedhi (GILD).

Nguva yekutengesa: Yakagamuchirwa neFDA yekutengesa muna Gumiguru 2017;Fosun Kite yakaunza Yescarta tekinoroji kubva kuKite Pharma ndokuigadzira kuChina mushure mekuwana mvumo.Yakatenderwa kunyorwa munyika.

Zviratidzo: Pakurapa kwekudzokazve kana kuti refractory hombe B-cell lymphoma.

Remarks: Yescarta mushonga weretroviral in vitro gene therapy, inova yechipiri yakatenderwa kurapwa kweCAR-T pasi rose.Inonangana neCD19 uye inotora costimulator yeCD28.Inotengeswa pa $373,000 muUnited States.

(8) Tecartus

Kambani: Yakagadzirwa neGiriyedhi (GILD).

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Chikunguru 2020.

Zviratidzo: Zvekudzokazve kana refractory mantle cell lymphoma.

Mashoko: Tecartus ndeye autologous CAR-T cell therapy yakanangana neCD19, uye ndiyo yechitatu CAR-T kurapwa yakabvumidzwa kushambadzira munyika.

(9) Breyanzi

COMPANY: Yakagadzirwa neBristol-Myers Squibb (BMS).

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Kukadzi 2021.

Zviratidzo: Yakadzoka zvakare kana kuti refractory (R / R) yakakura B-cell lymphoma (LBCL).

Remarks: Breyanzi in vitro gene therapy yakavakirwa pa lentivirus, yechina CAR-T therapy inotenderwa kushambadzira munyika, yakanangana neCD19.Kubvumidzwa kwaBreyanzi chiitiko chakakosha cheBristol-Myers squibb mumunda we cellular immunotherapy, iyo yaakawana payakawana Celgene yemabhiriyoni makumi manomwe nemana emadhora muna 2019.

(10) Abecma

Kambani: Co-yakagadziridzwa naBristol-Myers Squibb (BMS) uye bluebird bio.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira munaKurume 2021.

Zviratidzo: kudzokororwa kana kuti refractory multiple myeloma.

Mashoko: Abecma in vitro gene therapy yakavakirwa pa lentivirus, yekutanga pasi rose CAR-T cell therapy yakanangana neBCMA, uye yechishanu CAR-T kurapa kwakabvumidzwa neFDA.Nheyo yemushonga ndeyekutaura chimeric BCMA receptors pamasero eT emurwere kuburikidza nelentivirus-mediated gene modification in vitro.Kurapa kubvisa asina genetically modified T masero muvarwere, uye wodzoreredza akagadziridzwa T masero, ayo anotsvaga nekuuraya BCMA-anoratidza cancer maseru muvarwere.

(11) Libmeldy

COMPANY: Yakagadzirwa neOrchard Therapeutics.

Nguva yemusika: Yakatenderwa neEuropean Union kuti inyore muna Zvita 2020.

Zvinoratidza: Pakurapa metachromatic leukodystrophy (MLD).

Remarks: Libmeldy ijena therapy yakavakirwa pa autologous CD34+ masero akagadziridzwa mu vitro ne lentivirus.Data yekiriniki inoratidza kuti imwe intravenous infusion yeLibmeldy inogona kunyatso shandura nzira yekutanga-yekutanga MLD kana ichienzaniswa neyakaomesesa mota uye yekuziva kukanganisa muvarwere vasina kurapwa vezera rimwe chete.

(12) Benoda

Kambani: Yakagadzirwa naWuXi Giant Nuo.

Nguva yemusika: Zvakatenderwa zviri pamutemo neNMPA munaGunyana 2021.

Zviratidzo: Kurapa kwevarwere vakura vane kudzokazve kana kuti refractory yakakura B-cell lymphoma (r / r LBCL) mushure mechipiri-mutsara kana pamusoro pe systemic therapy.

Manzwiro: Beinoda ndeye anti-CD19 CAR-T gene therapy, uye zvakare iri musimboti chigadzirwa cheWuXi Juro Company.Ndiyo yechipiri CAR-T chigadzirwa chakatenderwa kuChina, kunze kwekudzokororwa/refractory hombe B-cell lymphoid WuXi Giant Nuo inorongawo kugadzira Regiorensai jekiseni rekurapa mamwe akawanda anoratidza, anosanganisira follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) , yechipiri-mutsara weBBC lympho diffuse (DLL lymphostic hombe) lymphoma yakakura uye DALL lymphoma yakakura.

(13) CARVYKTI

Kambani: Chigadzirwa chekutanga cheLegend Biotech chakabvumidzwa kushambadzira.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Kukadzi 2022.

Zviratidzo: zvekurapa kwekudzokazve kana kuti refractory multiple myeloma (R / R MM).

Tsanangudzo: CARVYKTI (ciltacabtagene autoleucel, Cilta-cel kwenguva pfupi) iCAR-T cell immune gene therapy ine masoja maviri e-single-domain akananga kuB-cell maturation antigen (BCMA).Dhiyabhorosi inoratidza kuti CARVYKTI Mune varwere vane kudzokazve kana kuti refractory multiple myeloma vakagamuchira mana kana kupfuura mamwe maitiro ekurapa (kusanganisira proteasome inhibitors, immunomodulators uye anti-CD38 monoclonal antibodies), huwandu hwekupindura huwandu hwe98% hwakaratidzwa.

(14)Ebvallo

COMPANY: Yakagadziridzwa neAtara Biotherapeutics.

European Commission (EC) yekushambadzira muna Zvita 2022, ndiyo yekutanga pasi rose T cell therapy yakabvumidzwa kushambadzira.

Zviratidzo: Senge monotherapy yeEpstein-Barr virus (EBV)-inoenderana ne-post-transplantation lymphoproliferative disease (EBV+PTLD), varwere vanowana kurapwa vanofanira kunge vari vanhu vakuru nevana vanopfuura makore maviri avo vakambogamuchira imwe imwe mishonga yemishonga.

Tsanangudzo: Ebvallo inonzi allogeneic EBV-specific universal T-cell gene therapy inotarisa uye inobvisa masero ane EBV ane utachiona nenzira yeHLA-inorambidzwa.Kubvumidzwa kwekurapa uku kunobva pamhedzisiro yechikamu chakakosha chechitatu chekuongorora kwekiriniki, uye mhedzisiro yakaratidza kuti ORR yeboka reHCT neboka reSOT raive 50%.Muyero wakakwana wekuregererwa (CR) waiva 26.3%, chikamu chekuregererwa (PR) chiyero chaiva 23.7%, uye nguva yepakati yekuregererwa (TTR) yaiva mwedzi 1.1.Pakati pevarwere ve19 vakawana kuregererwa, gumi nemumwe aive nenguva yekupindura (DOR) yeinopfuura mwedzi mitanhatu.Mukuwedzera, maererano nekuchengeteka, hapana maitiro asina kunaka akadai segraft-versus-host disease (GvHD) kana Ebvallo-yakabatana cytokine release syndrome yakaitika.

2. In vivo gene therapy inobva pahutachiona hwehutachiona

(1) Gendicine/Jin Sheng

Kambani: Yakagadzirwa neShenzhen Saibainuo Kambani.

Nguva yemusika: Yakatenderwa kunyorwa muChina muna 2003.

Zviratidzo: Kurapa kwemusoro nemutsipa squamous cell carcinoma.

Cherechedza: Recombinant human p53 adenovirus injection Gendicine/Jinyousheng mushonga weadenovirus vector gene therapy une kodzero dzakazvimirira dzepfuma yeShenzhen Saibainuo Company.Rudzi rwevanhu 5 adenovirus inoumbwa neadenovirus yerudzi rwevanhu 5. Iyo yekare ndiyo inonyanya kugadziriswa ye-anti-tumor effect yemishonga, uye iyo yekupedzisira inonyanya kuita semutakuri.Iyo adenovirus vector inotakura therapeutic gene p53 kupinda muchitokisi chinotarirwa, inoratidzira bundu suppressor gene p53 musero rinotarirwa, uye gene expression Chigadzirwa chacho chinogona kukwidza-kugadzirisa zvakasiyana-siyana zvekurwisa cancer majini uye pasi-kutonga mabasa emhando dzakasiyana-siyana dze oncogenes, nekudaro zvichiwedzera kuuraya chinangwa chemuviri uye bundu mhedzisiro.

(2) Rigvir

Kambani: Yakagadzirwa neLatima Kambani, Latvia.

Nguva yekunyora: Yakatenderwa kunyorwa muLatvia muna 2004.

Zviratidzo: Pakurapa melanoma.

Remarks: Rigvir mushonga wegene wakavakirwa pane genetically modified ECHO-7 enterovirus vector.Parizvino, mushonga uyu wakagamuchirwa muLatvia, Estonia, Poland, Armenia, Belarus, nezvimwewo, uye zvakare iri kunyoreswa EMA munyika dzeEU.Mhosva dzekiriniki mumakore gumi apfuura dzakaratidza kuti hutachiona hweRigvir oncolytic hwakachengeteka uye hunoshanda, uye hunogona kuwedzera huwandu hwekupona kwevarwere vemelanoma ka4-6.Pamusoro pezvo, kurapa uku kunoshandawo kune akasiyana mamwe magomarara, anosanganisira colorectal cancer, pancreatic cancer, dundira cancer, kenza yeitsvo, kenza yeprostate, yemapapu, uterine cancer, lymphosarcoma, nezvimwe.

(3) Oncorine

Kambani: Yakagadzirwa neShanghai Sanwei Biological Company.

Nguva yemusika: Yakatenderwa kunyorwa muChina muna 2005.

Zviratidzo: kurapwa kwemusoro nemutsipa bundu, kenza yechiropa, kenza yepancreatic, kenza yechibereko uye mamwe magomarara.

Mashoko: Oncorine (安科瑞) ndeye oncolytic virus gene therapy chigadzirwa chinoshandisa adenovirus semutakuri.Iyo oncolytic adenovirus inowanikwa, iyo inogona kunyatso dhinda mup53 gene kushomeka kana abnormal tumors, zvichitungamira kune lysis yebundu masero, nekudaro kuuraya bundu maseru.pasina kukuvadza masero akajairika.Zvidzidzo zvekiriniki zvakaratidza kuti Ankerui ine chengetedzo yakanaka uye inoshanda kune akasiyana siyana emamota akaipa.

(4) Glybera

Kambani: Yakagadziriswa neUniQure.

Nguva yemusika: Yakatenderwa kunyorwa muEurope muna 2012.

Zviratidzo: Kurapa kwe lipoprotein lipase kushomeka (LPLD) neyakaomarara kana inodzokororwa episodhi yepancreatitis kunyangwe yakanyatso kurambidzwa kudya kwemafuta.

Tsanangudzo: Glybera (alipogene tiparvovec) inonzi gene therapy drug inobva kuAAV, inoshandisa AAV semutakuri kuti ashandure chirwere chekurapa LPL mumasero emasumbu, kuitira kuti masero anoenderana anogona kubudisa imwe chiyero che lipoprotein lipase, Kuderedza chirwere ichi, kurapa uku kunoshanda kwenguva yakareba kwenguva yakareba (drug effect) inogona kugara kwenguva refu (drug effect).Mushonga wacho wakabviswa pamusika muna 2017. Chikonzero chekubviswa kwayo chingave chakabatana nezvinhu zviviri: kudhura kwepamusoro uye kudiwa kwemusika.Mari yepakati pekurapwa kwemushonga uyu yakakwira kusvika paUS$1 miriyoni, uye pari zvino murwere mumwe chete akatenga akaishandisa.Kunyange hazvo kambani yeinishuwarenzi yekurapa yakadzosera US$900,000 pairi, zvakare mutoro wakakura kukambani yeinishuwarenzi.Mukuwedzera, zviratidzo zvinotarirwa nemishonga hazviwanzoitiki, nehuwandu hwehuwandu hwehuwandu hwe1 mumamiriyoni e1 uye nehuwandu hwekusaziva.

(5) Imlygic

Kambani: Yakagadzirwa neAmgen.

Nguva yemusika: Muna 2015, yakabvumidzwa kunyorwa muUnited States neEuropean Union.

Zvinoratidza: Kurapwa kwemaronda e<em>melanoma asingagoni kubviswa zvachose nokuvhiyiwa.

Remarks: Imlygic is an attenuated herpes simplex virus type 1 iyo yakagadziridzwa ne genetic technology (kubvisa ICP34.5 uye ICP47 gene fragments, uye kuisa munhu granulocyte macrophage colony-stimulating factor GM-CSF gene muhutachiona) (HSV-1) oncolytic-approve virus ndiyo yekutanga FDA therapy.Nzira yekutonga ndeye intralesional jekiseni, iyo inogona kuiswa zvakananga mumaronda e-melanoma kuti iite kuputika kwemasero emarara, kusunungura tumor-derived antigens uye GM-CSF, uye kukurudzira anti-tumor immune response.

(6) Luxturna

Kambani: Yakagadziridzwa neSpark Therapeutics, inotsigira yeRoche.

Nguva yemusika: Yakatenderwa kushambadzira neFDA muna 2017, ndokuzobvumidzwa kushambadzira muEurope muna 2018.

Zviratidzo: Kurapa kwevana nevakuru vakarasikirwa nemaonero nekuda kwekaviri-kopi RPE65 gene mutations asi vanochengetedza nhamba yakakwana yemasero eretinal.

Matauriro: Luxturna ndeye AAV-yakavakirwa gene therapy inotungamirwa ne subretinal jekiseni.The gene therapy inoshandisa AAV2 semutakuri kuunza kopi inoshanda yeyakajairika RPE65 gene mumasero eretinal emurwere, kuitira kuti masero anowirirana aratidze yakajairika RPE65 protein, achigadzira kushayikwa kweprotein yemurwere RPE65, nekudaro anovandudza kuona kwemurwere.

(7) Zolgensma

Kambani: Yakagadziridzwa neAveXis, inotsigira yeNovartis.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Chivabvu 2019.

Zviratidzo: Kurapa kweSpinal Muscular Atrophy (SMA) varwere vari pasi pemakore maviri.

Mazwi: Zolgensma ijena rekurapa rakavakirwa paAAV vector.Mushonga uyu ndiwo wega-nguva imwe chete chirongwa chekurapa chespinal muscular atrophy chakabvumidzwa kushambadzira munyika.Kutangwa kwemushonga kunovhura nguva itsva mukurapwa kwespinal muscular atrophy.peji, kufambira mberi kukuru.Iyi gene therapy inoshandisa scAAV9 vector kuunza yakajairika SMN1 gene mumurwere kuburikidza ne intravenous infusion kuti ibudise yakajairwa SMN1 protein, nekudaro inovandudza kushanda kwemaseru akakanganisika akadai semotor neurons.Kusiyana neizvi, mishonga yeSMA Spinraza neEvrysdi inoda nguva refu inodzokororwa dosing.Spinraza inopiwa nejekiseni remuzongoza mwedzi mina yega yega, uye Evrysdi mushonga unonwa zuva nezuva.

(8) Delytact

Kambani: Yakagadzirwa neDaiichi Sankyo Company Limited (TYO: 4568).

Nguva yemusika: Mvumo ine mamiriro kubva kuJapan Ministry of Health, Labor and Welfare (MHLW) muna Chikumi 2021.

Zvinoratidza: Zvekurapa malignant glioma.

Matauriro: Delytact ndiyo yechina oncolytic hutachiona gene therapy chigadzirwa chakabvumidzwa pasi rose, uye yekutanga oncolytic hutachiona chigadzirwa chakabvumidzwa kurapwa kwemalignant glioma.Delytact is a genetically engineered herpes simplex virus type 1 (HSV-1) oncolytic virus yakagadzirwa naDr. Todo nevamwe vaaishanda navo.Delytact inounza kumwe kudzima shanduko muG207 genome yechizvarwa chechipiri HSV-1, ichiwedzera kudzokororwa kwayo kwakasarudzika mumaseru egomarara uye kuiswa kweanopesana netumor immune mhinduro uchichengetedza kuchengetedzwa kwakanyanya.Delytact ndiyo yekutanga chizvarwa chechitatu oncolytic HSV-1 parizvino iri kuongororwa nekiriniki.Mvumo yeDelytact muJapan inonyanya kuenderana nechikamu chechipiri chekiriniki yekuedza kwechipatara.Mune varwere vane inodzokororwa glioblastoma, Delytact yakawana yekutanga kupera kwegore rimwe chete rekurarama, uye mhedzisiro yakaratidza kuti Delytact yakaratidza kuita zvirinani zvichienzaniswa neG207.Simba replicative rakasimba uye yakakwirira antitumor chiitiko.Izvi zvaishanda mumhando dzakasimba dzebundu rezamu, prostate, schwannomas, nasopharyngeal, hepatocellular, colorectal, malignant peripheral nerve sheath tumors, uye gomarara rethyroid.

(9) Upstaza

COMPANY: Yakagadzirwa nePTC Therapeutics, Inc. (NASDAQ: PTCT).

Nguva yemusika: Yakatenderwa neEuropean Union yekushambadzira muna Chikunguru 2022.

Zviratidzo: Pakushomeka kweL-amino acid decarboxylase (AADC) inonhuhwirira, inotenderwa kurapwa kwevarwere vane mwedzi gumi nemasere zvichikwira.

Mashoko: Upstaza™ (eladocagene exuparvovec) iri mu vivo gene therapy ine adeno-yakabatana utachiona rudzi 2 (AAV2) semutakuri.Varwere vanorwara nekuda kwekuchinja-chinja kwejeni inokodha iyo AADC enzyme.AAV2 inotakura gene ine hutano inokodha iyo AADC enzyme.Chimiro chemuripo wejini chinowana mushonga wekurapa.Muchirevo, humwe hutongi hunoshanda kwenguva yakareba.Ndiyo yekutanga inotengeswa gene therapy iyo inobaiwa zvakananga muuropi.Mvumo yekushambadzira inoshanda kune ese makumi maviri nenomwe enhengo dzeEU, pamwe neIceland, Norway neLiechtenstein.

(10) Roctavian

Kambani: Yakagadzirwa neBioMarin Pharmaceutical (BioMarin).

Nguva yemusika: Yakatenderwa kushambadzira neEuropean Union muna Nyamavhuvhu 2022;mvumo yekushambadzira neUK Medicines uye Healthcare products Administration (MHRA) muna Mbudzi 2022.

Zviratidzo: Kurapa varwere vakuru vane hemophilia yakaoma A vasina nhoroondo yeFVIII factor inhibition uye vari negative kune AAV5 antibodies.

Mashoko: Roctavian (valoctocogene roxaparvovec) inoshandisa AAV5 sevheji uye inoshandisa chiropa chemunhu chakananga HLP kufambisa kutaura kwehuman coagulation factor VIII (FVIII) ine B domain yakabviswa.Sarudzo yeEuropean Commission yekubvumidza kutengeswa kwevaloctocogene roxaparvovec yakavakirwa pane data rese rechirongwa chekuvandudza mushonga.Pakati pavo, migumisiro yechikamu chechitatu chekliniki yekuedza GENER8-1 yakaratidza kuti kana ichienzaniswa nedheta regore risati ranyorwa, mushure mokunge imwe chete infusion ye valoctocogene roxaparvovec, Musoro wegore negore wekubuda ropa (ABR) wakaderedzwa zvakanyanya, kuwanda kwekushandiswa kwe recombinant coagulation factor VIII (F8) mapuroteni ekugadzirira kunoderedzwa, kana kuti basa reropa reF8 rinowedzera zvakanyanya mumuviri.Mushure memavhiki e4 ekurapwa, chiyero chegore negore chekushandisa F8 uye ABR inoda kurapwa yakaderedzwa ne 99% uye 84%, maererano, uye mutsauko wakanga wakakosha (p <0.001).Nhoroondo yekuchengeteka yakanga yakanaka, uye hapana nyaya yakasangana neF8 factor inhibition, kuipa kana thrombosis side effects, uye hapana zviitiko zvakakomba zvine chokuita nekurapa (SAEs) zvakataurwa.

(11) Hemgenix

Kambani: Yakagadzirwa neUniQure Corporation.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Mbudzi 2022.

Zviratidzo: Kurapa kwevarwere vakuru vane hemophilia B.

Matauriro: Hemgenix ijena rekurapa rakavakirwa paAAV5 vector.Mushonga uyu wakashongedzerwa neiyo coagulation factor IX (FIX) gene mutsauko FIX-Padua, iyo inopihwa mutsinga.Mushure mekutonga, jini rinogona kuratidza iyo FIX coagulation factor muchiropa uye yakavanzika Mushure mekupinda muropa kuti iite coagulation basa, kuitira kuti iwane chinangwa chekurapa, inotaura, imwe hutungamiri hunoshanda kwenguva yakareba.

(12) Adstiladrin

Kambani: Yakagadzirwa neFerring Pharmaceuticals.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Zvita 2022.

Zviratidzo: Pakurapa kwepamusoro-soro yegomarara regomarara redundira (NMIBC) isingateereri Bacillus Calmette-Guerin (BCG) .

Mashoko: Adstiladrin ijena therapy yakavakirwa pane isingadzokorodze adenoviral vector, inogona overexpress interferon alfa-2b protein mumaseru anotariswa, uye inopihwa kuburikidza neurinary catheter mudundira (inopihwa kamwe chete mwedzi mitatu yega), hutachiona hwevhavha hunogona kunyatsopinda mumaseru e-bladder uye kuputika kweprotein. utic effect.Iyi nzira itsva yekurapa majini nokudaro inoshandura masero omudhuri wedundira kuti ave “fekitari” duku inobudisa interferon, nokudaro zvichiita kuti murwere akwanise kurwisa kenza.

Kuchengetedzwa uye kushanda kweAdstiladrin kwakaongororwa mune yakawanda yekiriniki yekudzidza kusanganisira varwere ve157 vane ngozi yakawanda BCG-isingateereri NMIBC.Varwere vakagamuchira Adstiladrin mwedzi mitatu yega yega kusvika kumwedzi ye12, kana kusvika kusingagamuchirwe chepfu mukurapwa kana kudzoka kwepamusoro-giredhi NMIBC.Pakazara, 51 muzana yevarwere vakanyoresa vakarapwa neAdstiladrin vakawana mhinduro yakakwana (kunyangarika kwezviratidzo zvese zvegomarara zvinoonekwa pacystoscopy, biopsy tishu, uye weti).

3. Small nucleic acid mishonga

(1) Vitravene

Kambani: Yakabatanidzwa neIonis Pharma (yaimbova Isis Pharma) uye Novartis.

Nguva yemusika: Muna 1998 na1999, yakatenderwa kushambadzira neFDA neEU EMA.

Zviratidzo: Kurapa kwe cytomegalovirus retinitis muvarwere vane HIV.

Mashoko: Vitravene is an antisense oligonucleotide drug, iyo ndiyo yekutanga oligonucleotide mishonga inobvumirwa kutengeswa munyika.Pakutanga danho rekunyora, kudiwa kwemusika kwemishonga inorwisa CMV kwaikurumidzira;gare gare, nokuda kwekugadzirwa kwemishonga inorwisa mabhakitiriya, nhamba yezviitiko zve CMV yakaderera zvakanyanya.Nekuda kwekushomeka kwemusika, mushonga wakatangwa muna 2002 uye 2006 Kubviswa munyika dzeEU neUnited States.

(2) Macugen

Kambani: Co-yakagadziridzwa naPfizer uye Eyetech.

Nguva yemusika: Yakatenderwa kunyorwa muUnited States muna 2004.

Zviratidzo: Pakurapa neovascular age-related macular degeneration.

Tsanangudzo: Macugen is pegylated modified oligonucleotide drug, iyo inogona kutarisa uye kusunga vascular endothelial growth factor (VEGF165 subtype), uye nzira yekutonga ndeye intravitreal injection.

(3) Defitelio

Kambani: Yakagadziriswa neJazz Pharmaceuticals.

Nguva yemusika: Yakatenderwa kushambadzira neEuropean Union muna 2013 uye yakatenderwa neFDA kushambadzira muna Kurume 2016.

Zviratidzo: Kurapa kwehepatic veno-occlusive chirwere chakabatana nerenal kana pulmonary dysfunction mushure mekuita hematopoietic stem cell transplantation.

Tsanangudzo: Defitelio inonzi oligonucleotide drug, iyo inosanganiswa ye oligonucleotides ine plasmin properties.Yakabviswa pamusika muna 2009 nekuda kwezvikonzero zvekutengesa.

(4) Kynamro

Kambani: Co-yakagadziridzwa naIonis Pharma naKastle.

Nguva yemusika: Muna 2013, yakatenderwa kushambadzira muUnited States semushonga wenherera.

Zvinoratidza: Zvekurapa adjuvant ye homozygous mhuri hypercholesterolemia.

Tsanangudzo: Kynamro is an antisense oligonucleotide drug, iri antisense oligonucleotide inotarisa munhu apo B-100 mRNA.Kynamro inoshandiswa se 200 mg subcutaneously kamwe pavhiki.

(5) Spinraza

Kambani: Yakagadziriswa neIonis Pharmaceuticals.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Zvita 2016.

Zviratidzo: Kurapa kwespinal muscular atrophy (SMA).

Tsanangudzo: Spinraza (nusinersen) is antisense oligonucleotide drug.Nekusunga kune cleavage saiti yeSMN2 exon 7, Spinraza inogona kushandura iyo RNA cleavage yeSMN2 gene, nekudaro ichiwedzera kugadzirwa kweanoshanda zvizere SMN protein.Muna Nyamavhuvhu 2016, BIOGEN yakashandisa sarudzo yayo kuwana kodzero dzepasi rose kuSpinraza.Spinraza yakangotanga kuyedza kwekutanga kwekiriniki muvanhu mu2011. Mumakore mashanu chete, yakabvumidzwa neFDA yekushambadzira mu2016, iyo inoratidza iyo FDA izere kucherechedzwa kwekuita kwayo.Mushonga uyu wakabvumidzwa kushambadzira muChina muna Kubvumbi 2019. Kutenderera kwese kwemvumo yeSpinraza muChina kwaive isingasviki mwedzi mitanhatu, uye yaive makore maviri nemwedzi miviri kubva Spinraza yakatanga kubvumidzwa muUnited States.Iko kumhanya kwekunyora muChina kwatove nekukurumidza.Izvi zvinokonzerwawo nenyaya yekuti Center for Drug Evaluation yakapa "Chiziviso cheKutsikisa Rondedzero yeBatch Yekutanga yeOverseas New Drugs Inodiwa Nekukurumidza muClinical Practice" musi waNovember 1, 2018, uye yakaverengerwa muboka rekutanga remishonga mitsva makumi mana yekune dzimwe nyika yekukurumidzira kuongororwa, pakati peiyo Spinraza yakaiswa mukati.

(6) Eksodho 51

Kambani: Yakagadzirwa neAVI BioPharma (yakazonzi Sarepta Therapeutics).

Nguva yemusika: MunaGunyana 2016, yakatenderwa kushambadzira neFDA.

Zviratidzo: Kurapa kweDuchenne muscular dystrophy (DMD) ne exon 51 kusvetuka gene mutation muDMD gene.

Tsanangudzo: Exondys 51 is an antisense oligonucleotide drug, iyo antisense oligonucleotide inogona kusunga panzvimbo ye exon 51 ye-pre-mRNA yeDMD gene, zvichiita kuti pave nekugadzirwa kwemRNA yakakura, chikamu che exon 51 chakavharwa Excision, nekudaro kugadzirisa zvishoma mapuroteni ekugadzirisa mapuroteni ekugadzirisa mRNA mapfupi ekugadzirisa mapuroteni ekugadzirisa mRNA. , nokudaro kuvandudza zviratidzo zvemurwere.

(7) Tegsedi

Kambani: Yakagadziriswa neIonis Pharmaceuticals.

Nguva yemusika: Yakatenderwa kushambadzira neEuropean Union muna Chikunguru 2018.

Zviratidzo: Pakurapa kwenhaka transthyretin amyloidosis (hATTR).

Tsanangudzo: Tegsedi inonzi antisense oligonucleotide drug inotarisa transthyretin mRNA.Ndiwo mushonga wekutanga unobvumidzwa munyika kurapa hATTR.Inoitwa ne subcutaneous injection.Mushonga unoderedza kugadzirwa kweATTR protein nekutarisa mRNA ye transthyretin (ATTR), uye ine mukana wakanaka wengozi mukurapa kweATTR, uye chirwere chepfungwa chemurwere uye hupenyu hwehupenyu zvakagadziridzwa zvakanyanya, uye zvinopindirana neTTR mutation marudzi, Hapana danho rechirwere kana kuvapo kwecardiomyopathy yakanga yakakosha.

(8) Onpattro

Kambani: Yakabatanidzwa neAlnylam Corporation uye Sanofi Corporation.

Nguva yemusika: Yakatenderwa kunyorwa muUnited States muna 2018.

Zviratidzo: Pakurapa kwenhaka transthyretin amyloidosis (hATTR).

Tsanangudzo: Onpattro is an siRNA drug inotarisa transthyretin mRNA, iyo inoderedza kugadzirwa kweATTR protein muchiropa uye inoderedza kuunganidzwa kweamyloid deposits mu peripheral nerve nekutarisa mRNA ye transthyretin (ATTR) , nokudaro kuvandudza uye kuderedza zviratidzo zvechirwere.

(9) Givlaari

Kambani: Yakagadzirwa neAlnylam Corporation.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira munaNovember 2019.

Zviratidzo: Kurapa kweacute hepatic porphyria (AHP) muvakuru.

Mashoko: Givlaari mushonga we siRNA, inova yechipiri siRNA mushonga unobvumidzwa kushambadzira mushure meOnpattro.Nzira yekutonga ndeye subcutaneous jekiseni.Mushonga wacho unonangana nemRNA yeALAS1 protein, uye kurapwa kwemwedzi neGivlaari kunogona kuderedza zvakanyanya uye zvachose mwero weALAS1 muchiropa, nekudaro kuderedza mazinga eurotoxic ALA nePBG kusvika kune yakajairika, nekudaro Kuderedza zviratidzo zvechirwere chemurwere.Iyo data yakaratidza kuti varwere vanobatwa neGivlaari vaive ne74% kuderedzwa kwenhamba yekubatwa vachienzanisa neboka re placebo.

(10) Vyondys53

COMPANY: Yakagadziriswa neSarepta Therapeutics.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Zvita 2019.

Zviratidzo: Kurapa kwevarwere veDMD vane dystrophin gene exon 53 splicing mutation.

Tsanangudzo: Vyondys 53 is an antisense oligonucleotide drug, iyo inotarisa splicing process ye dystrophin pre-mRNA.Exon 53 yakaderedzwa zvishoma, kureva kuti haipo pamRNA yakakura, uye yakagadzirirwa kuburitsa diki asi ichiri kushanda dystrophin, nekudaro ichivandudza kugona kwekurovedza muviri muvarwere.

(11) Waylivra

Kambani: Yakagadziridzwa neIonis Pharmaceuticals uye inotsigira Akcea Therapeutics.

Nguva yemusika: Yakatenderwa kushambadzira neEuropean Medicines Agency (EMA) muna Chivabvu 2019.

Zviratidzo: Semushonga we adjuvant mukuwedzera kukudzora kwekudya muvarwere vakuru vane mhuri chylomicronemia syndrome (FCS).

Tsanangudzo: Waylivra is an antisense oligonucleotide drug, inova ndiyo yekutanga mishonga inobvumirwa kutengeswa munyika kuitira kurapwa kweFCS.

(12) Leqvio

Kambani: Yakagadzirwa naNovartis.

Nguva yemusika: Yakatenderwa neEuropean Union yekushambadzira muna Zvita 2020.

Zviratidzo: Kurapa kwevakuru vane primary hypercholesterolemia (heterozygous mhuri uye isiri yemhuri) kana yakasanganiswa dyslipidemia.

Mashoko: Leqvio mushonga we siRNA wakanangana nePCSK9 mRNA.Ndiyo yekutanga pasi rose siRNA kurapa kwekudzikisa cholesterol (LDL-C).Inoitwa ne subcutaneous injection.Mushonga unoderedza chiyero chePCSK9 protein kuburikidza neRNA kupindira, nokudaro kuderedza chiyero cheLDL-C.Data yekiriniki inoratidza kuti kuvarwere vasingakwanise kudzikisa mazinga eLDL-C kusvika padanho rakanangwa mushure mekurapwa neiyo yakanyanya kubvumidzwa dosi yema statins, Leqvio inogona kuderedza LDL-C ne50%.

(13)Oxlumo

Kambani: Yakagadzirwa neAlnylam Pharmaceuticals.

Nguva yemusika: Yakatenderwa neEuropean Union yekushambadzira munaNovember 2020.

Zviratidzo: Pakurapa kwekutanga hyperoxaluria mhando 1 (PH1).

Tsanangudzo: Oxlumo mushonga weSiRNA wakanangana nehydroxyacid oxidase 1 (HAO1) ​​mRNA, uye nzira yekutonga ndeye subcutaneous jekiseni.Mushonga uyu wakagadzirwa uchishandisa Alnylam ichangoburwa yakawedzera kudzikamisa chemistry, ESC-GalNAc conjugation tekinoroji, iyo inogonesa subcutaneously kupihwa siRNA nekushingirira kukuru uye potency.Mushonga wacho unosvibisa kana kuti inhibits hydroxyacid oxidase 1 (HAO1) ​​mRNA, inoderedza chiyero che glycolate oxidase muchiropa, uye inopedza substrate inodiwa pakugadzirwa kweoxalate, kuderedza kugadzirwa kweoxalate kudzora kufambira mberi kwechirwere muvarwere nekuvandudza zviratidzo zvechirwere.

(14) Viltepso

Kambani: Yakagadzirwa neNS Pharma, inotsigira yeNippon Shinyaku.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Nyamavhuvhu 2020.

Zviratidzo: Kurapa kweDuchenne muscular dystrophy (DMD) ne exon 53 kusvetuka gene mutation muDMD gene.

Tsanangudzo: Viltepso is an antisense oligonucleotide drug inogona kusunga panzvimbo ye exon 53 ye-pre-mRNA yeDMD gene, zvichiita kuti chikamu che exon 53 chicheneswe mushure mekuumbwa kwemRNA yakakura, nokudaro kugadzirisa zvishoma mRNA kuverenga furemu Bhokisi rinobatsira varwere kuti vagadzirise mamwe maitiro eprotein anowanikwa mapuroteni mapfupi, mapuroteni anowanikwa kune mamwe mapuroteni anowanikwa.

(15) Amondi makumi mana neshanu

Kambani: Yakagadzirwa neSarepta Therapeutics.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Kukadzi 2021.

Zviratidzo: Kurapa kweDuchenne muscular dystrophy (DMD) ne exon 45 kusvetuka gene mutation muDMD gene.

Tsanangudzo: Amondys 45 is an antisense oligonucleotide drug, antisense oligonucleotide inogona kusunga panzvimbo ye exon 45 ye pre-mRNA yeDMD gene, zvichiita kuti chikamu che exon 45 chivharwe mushure mekuumbwa kwekukura mRNA Excision, nokudaro zvishoma nezvishoma kushandura mafomu ekugadzirisa maitiro ekugadzirisa mRNA kupfupika kwemRNA mafomu ekugadzirisa mapfupi ekugadzirisa mRNA. mapuroteni, nokudaro achivandudza zviratidzo zvemurwere.

(16) Amvuttra (vutrisiran)

Kambani: Yakagadzirwa neAlnylam Pharmaceuticals.

Nguva yemusika: Yakatenderwa neFDA yekushambadzira muna Chikumi 2022.

Zviratidzo: Kurapwa kwenhaka transthyretin amyloidosis ine polyneuropathy (hATTR-PN) muvakuru.

Tsanangudzo: Amvuttra (Vutrisiran) mushonga we siRNA wakanangana ne transthyretin (ATTR) mRNA, inotungamirwa nejekiseni repasi.Vutrisiran yakavakirwa paAlnylam's Enhanced Stability Chemistry (ESC)-GalNAc conjugate delivery platform dhizaini nekuwedzera potency uye metabolic kugadzikana.Mvumo yekurapa inobva pamashoko emwedzi we9 weChikamu chechitatu chekliniki yekudzidza (HELIOS-A), uye migumisiro yose inoratidza kuti kurapa kwakavandudza zviratidzo zvehATTR-PN, uye kupfuura 50% yehutano hwevarwere hwakadzorerwa kana kumira kubva pakuipa.

4. Mamwe magene therapy mishonga

(1) Rexin-G

Kambani: Yakagadzirwa neEpeius Biotech.

Nguva yemusika: Muna 2005, yakatenderwa kushambadzira nePhilippine Food and Drug Administration (BFAD).

Zviratidzo: Kurapwa kwekenza yepamusoro inopesana nechemotherapy.

Mazwi: Rexin-G ijene-rakatakura nanoparticle jekiseni.Inosuma iyo cyclin G1 mutant gene mumaseru anotangwa kuburikidza neretroviral vector kuti iuraye chaizvo mamota akasimba.Iyo nzira yekutonga ndeye intravenous infusion.Semushonga wakanangwa nebundu uyo ​​unoshingairira kutsvaga nekuparadza metastatic cancer maseru, ine imwe mhedzisiro yekurapa kune varwere vakakundikana mamwe mishonga yegomarara, kusanganisira yakanangwa biologics.

(2) Neovasculgen

Kambani: Yakagadzirwa neHuman stem cell Institute.

Nguva yekunyora: Yakatenderwa kunyorwa muRussia muna Zvita 7, 2011, uye yakazotangwa muUkraine muna 2013.

Zvinoratidza: Kurapa kweperipheral vascular arterial disease, kusanganisira yakaoma nhengo ischemia.

Matauriro: Neovasculgen ijena rekurapa rakavakirwa paDNA plasmids.Iyo vascular endothelial growth factor (VEGF) 165 gene inovakwa pamusana weplasmid uye inopinzwa muvarwere.

(3) Collategene

Kambani: Yakabatanidzwa neOsaka University uye venture capital makambani.

Nguva yemusika: Yakatenderwa neBazi reHutano, Basa uye Hupenyu hweJapan muna Nyamavhuvhu 2019.

Zviratidzo: Kurapa kweyakanyanya kuderera kwekupedzisira ischemia.

Tsanangudzo: Collategene iplasmid-based gene therapy, yekutanga mudzimba gene therapy mushonga unogadzirwa neAnGes, kambani yegene therapy muJapan.Chinhu chikuru chemushonga uyu iplasmid isina kupfeka ine munhu hepatocyte growth factor (HGF) gene sequence.Kana mushonga wacho wakaiswa mumisumbu yemakumbo ezasi, iyo inoratidzwa HGF inosimudzira kuumbwa kwetsinga itsva dzeropa dzakatenderedza tsinga dzeropa dzakavharika.Miedzo yemakiriniki yakasimbisa kushanda kwayo pakuvandudza maronda.

Ko Foregene inogona kubatsira sei gene therapy kukura?

Isu tinobatsira kuchengetedza nguva yekuongorora muhukuru hwekuongorora, padanho rekutanga reSiRNA kugadzirwa kwezvinodhaka.

Mamwe mashoko shanya:

https://www.foreivd.com/cell-direct-rt-qpcr-kit-direct-rt-qpcr-series/