Posachedwapa, mankhwala atatu ochizira majini avomerezedwa kuti azigulitsidwa, omwe ndi: (1) Pa Julayi 21, 2022, PTC Therapeutics, Inc. (NASDAQ: PTCT) idalengeza kuti AAV gene therapy Upstaza™ idavomerezedwa ndi European Commission Ndiwoyamba kugulitsidwa mankhwala a jini omwe amabayidwa mwachindunji muubongo (onani nkhani zam'mbuyomu mu Generapy ubongo umaloledwa kugulitsa).(2) Pa Ogasiti 17, 2022, US Food and Drug Administration (FDA) idavomereza Bluebird Bio's gene therapy Zynteglo (betibeglogene autotemcel, beti-cel) yochizira beta thalassemia.Kuvomerezedwa kwa mankhwalawa ku United States mosakayikira ndi "thandizo mu chisanu" kwa Bluebird Bio, yomwe ili pamavuto azachuma.(3) Pa Ogasiti 24, 2022, BioMarin Pharmaceutical (BioMarin) idalengeza kuti European Commission idavomereza kutsatsa kokhazikika kwa ROCTAVIAN™ (valoctocogene roxaparvovec), mankhwala a jini a hemophilia A, pochiza odwala omwe alibe mbiri ya FVIII factor inhibitors ndi negative AAV5 hemophilia antibodies (akuluakulu a hemophilia AAV5) Chithandizo cha jini chovomerezeka kutsatsa).Pakadali pano, mankhwala 41 ochizira majini avomerezedwa kuti azitsatsa padziko lonse lapansi.

Gene ndiye gawo loyambira la chibadwa lomwe limawongolera mawonekedwe.Kupatulapo majini a mavairasi ena, omwe amapangidwa ndi RNA, majini a zamoyo zambiri amapangidwa ndi DNA.Matenda ambiri a zamoyo amayamba chifukwa cha kugwirizana kwa majini ndi chilengedwe, ndipo matenda ambiri amatha kuchiritsidwa kapena kuchepetsedwa kwenikweni kudzera mu chithandizo cha majini.Gene therapy imatengedwa ngati kusintha pazamankhwala ndi mankhwala.The yotakata jini mankhwala mankhwala monga mankhwala zochokera DNA-modified DNA mankhwala (monga mavairasi vekitala-based in vivo gene therapy mankhwala, in vitro gene therapy mankhwala, maliseche plasmid mankhwala, etc.) ndi RNA mankhwala (monga antisense oligonucleotide mankhwala, siRNA mankhwala, ndi mRNA gene therapy, etc.);Mankhwala odziwika bwino a Gene therapy makamaka amaphatikizapo mankhwala a plasmid DNA, mankhwala ochizira majini otengera ma virus, mankhwala ochizira ma gene otengera ma bacteria, makina osintha ma gene ndi mankhwala ochizira ma cell omwe amasinthidwa mu vitro.Pambuyo pazaka zambiri zachitukuko chovutitsa, mankhwala a gene therapy apeza zotsatira zolimbikitsa zachipatala.(kupatula katemera wa DNA ndi katemera wa mRNA), mankhwala 41 ochizira majini avomerezedwa kuti azigulitsidwa padziko lonse lapansi.Ndi kukhazikitsidwa kwa zinthu ndi chitukuko chofulumira chaukadaulo wa gene therapy, chithandizo cha majini chatsala pang'ono kuyambitsa nthawi yachitukuko chofulumira.

Gulu la chithandizo cha majini (Chitsime cha zithunzi: Biological Jingwei)

Nkhaniyi yatchula mitundu 41 yochizira ma jini yomwe yavomerezedwa kuti igulitsidwe (kupatula katemera wa DNA ndi katemera wa mRNA).

1. Chithandizo cha majini mu m'galasi

(1) Strimvelis

Kampani: Yopangidwa ndi GlaxoSmithKline (GSK).

Nthawi Yogulitsa: Yavomerezedwa ndi European Union mu Meyi 2016.

Zochizira kwambiri kuphatikiza immunodeficiency (SCID).

Ndemanga: Njira yayikulu ya mankhwalawa ndikutenga kaye maselo amtundu wa hematopoietic wa wodwalayo, kuwakulitsa ndi kuwakulitsa mu vitro, ndiyeno kugwiritsa ntchito retrovirus kuyambitsa jini yogwira ntchito ya ADA (adenosine deaminase) m'maselo awo a hematopoietic, ndipo pamapeto pake kusamutsa maselo osinthidwa a hematopoietic.Ma cell a hematopoietic stem amalowetsedwa m'thupi.Zotsatira zachipatala zidawonetsa kuti kupulumuka kwazaka zitatu kwa odwala ADA-SCID omwe amathandizidwa ndi Strimvelis kunali 100%.

(2) Zalmoxis

Kampani: Yopangidwa ndi MolMed, Italy.

Nthawi Yogulitsa: Analandira chilolezo chotsatsa chotsatira cha EU mu 2016.

Iwo ntchito adjuvant mankhwala a chitetezo cha m`thupi odwala pambuyo hematopoietic tsinde cell kupatsidwa zina.

Ndemanga: Zalmoxis ndi allogeneic T cell suicide gene immunotherapy yosinthidwa ndi retroviral vector.Ma jini odzipha a 1NGFR ndi HSV-TK Mut2 amalola anthu kugwiritsa ntchito ganciclovir nthawi iliyonse kupha maselo a T omwe amachititsa kuti chitetezo cha mthupi chitetezeke, kuteteza kuwonongeka kwa GVHD komwe kungachitike, ndikubwezeretsa chitetezo cha mthupi kwa odwala omwe ali ndi haploidentical HSCT pambuyo pa opaleshoni Escort.

(3) Invossa-K

Kampani: Yopangidwa ndi kampani ya TissueGene (KolonTissueGene).

Nthawi yogulitsa: Zavomerezedwa kuti zilembedwe ku South Korea mu Julayi 2017.

Zochizira osachiritsika bondo nyamakazi.

Ndemanga: Invossa-K ndi allogeneic cell gene therapy yomwe imaphatikizapo ma chondrocyte aumunthu.Maselo a allogeneic amasinthidwa mwachibadwa mu vitro, ndipo maselo osinthidwa amatha kufotokoza ndi kubisala kusintha kwa kukula kwa β1 (TGF-β1) pambuyo pa jekeseni wa intra-articular.β1), potero kukonza zizindikiro za osteoarthritis.Zotsatira zachipatala zikuwonetsa kuti Invossa-K imatha kusintha kwambiri nyamakazi ya mawondo.Layisensiyo idathetsedwa ndi woyang'anira mankhwala ku South Korea mu 2019 chifukwa wopanga adalemba molakwika zomwe zidagwiritsidwa ntchito.

(4) Zynteglo

Kampani: Yopangidwa ndi kampani ya American bluebird bio (bluebird bio) company.

Nthawi yogulitsa: Kuvomerezedwa ndi European Union mu 2019, ndikuvomerezedwa ndi FDA mu Ogasiti 2022.

Zochizira β-thalassemia yodalira magazi.

Ndemanga: Zynteglo ndi lentiviral in vitro gene gene therapy, yomwe imagwiritsa ntchito lentiviral vector kuti iwonetsetse jini yodziwika bwino ya β-globin (βA-T87Q-globin gene) m'maselo a hematopoietic ochotsedwa kwa odwala., ndiyeno kulowetsamo maselo amtundu wa autologous hematopoietic tsinde osinthidwa mwa odwala.Wodwalayo akakhala ndi jini yachibadwa ya βA-T87Q-globin, amatha kupanga mapuloteni abwinobwino a HbAT87Q, omwe amatha kuchepetsa kapena kuthetsa kufunikira kwa kuikidwa magazi.Ndi chithandizo chanthawi imodzi chomwe chimapangidwa kuti chilowe m'malo mwa kuthiridwa magazi kwa moyo wonse komanso mankhwala amoyo wonse kwa odwala azaka 12 kapena kuposerapo.

(5) Skysona

Kampani: Yopangidwa ndi kampani ya American bluebird bio (bluebird bio) company.

Nthawi yogulitsa: Adavomerezedwa ndi EU kuti azitha kutsatsa mu Julayi 2021.

Zochizira oyambirira cerebral adrenoleukodystrophy (CALD).

Ndemanga: Chithandizo cha jini cha Skysona ndi njira yokhayo yokhayo yovomerezeka yochizira matenda a cerebral cerebral adrenoleukodystrophy (CALD).Skysona (elivaldogene autotemcel, Lenti-D) ndi hematopoietic stem cell lentiviral in vitro gene therapy Lenti-D.Njira yonse ya mankhwalawa ndi iyi: maselo amtundu wa autologous hematopoietic amachotsedwa kwa wodwalayo, kusinthidwa mu vitro ndi lentivirus yomwe imanyamula jini ya ABCD1 yaumunthu, kenako imalowetsedwanso mwa wodwalayo.Zochizira odwala osakwana zaka 18 ndi ABCD1 gene mutation ndi CALD.

(6) Chimiriya

Kampani: Yopangidwa ndi Novartis.

Nthawi Yogulitsa: Yovomerezedwa ndi FDA mu Ogasiti 2017.

Chithandizo cha kalambulabwalo B-cell acute lymphoblastic leukemia (ALL) ndi kubwereranso ndi refractory DLBCL.

Ndemanga: Kymriah ndi mankhwala a lentiviral in vitro gene therapy, mankhwala oyamba ovomerezeka padziko lonse a CAR-T, olunjika ku CD19 komanso kugwiritsa ntchito co-stimulatory factor 4-1BB.Mitengo ndi $475,000 ku US ndi $313,000 ku Japan.

(7) Yescarta

Kampani: Yopangidwa ndi Kite Pharma, nthambi ya Gileadi.

Nthawi yogulitsa: Adavomerezedwa ndi FDA mu Okutobala 2017.

Zochizira anayambiranso kapena refractory lalikulu B-maselo lymphoma.

Ndemanga: Yescarta ndi retroviral in vitro gene therapy.Ndi chithandizo chachiwiri cha CAR-T chovomerezeka padziko lonse lapansi.Imalimbana ndi CD19 ndipo imagwiritsa ntchito costimulatory factor ya CD28.Mitengo ku US ndi $373,000.

(8) Tecartus

Kampani: Yopangidwa ndi Gileadi (GILD).

Nthawi yogulitsa: Yovomerezedwa ndi FDA mu Julayi 2020.

Kwa kubwereranso kapena refractory mantle cell lymphoma.

Ndemanga: Tecartus ndi autologous CAR-T cell therapy yolunjika ku CD19, ndipo ndi mankhwala achitatu a CAR-T omwe amavomerezedwa kuti azitsatsa padziko lonse lapansi.

(9) Breyanzi

Kampani: Yopangidwa ndi Bristol-Myers Squibb (BMS).

Nthawi yogulitsa: Kuvomerezedwa ndi FDA mu February 2021.

Zizindikiro: Kubwereranso kapena kukana (R / R) lalikulu B-cell lymphoma (LBCL).

Ndemanga: Breyanzi ndi in vitro gene therapy yochokera ku lentivirus, ndipo chithandizo chachinayi cha CAR-T chovomerezedwa kuti chizigulitsidwa padziko lonse lapansi, cholunjika ku CD19.Kuvomerezedwa kwa Breyanzi ndichinthu chofunikira kwambiri kwa Bristol-Myers Squibb pankhani ya ma immunotherapy, omwe Bristol-Myers adapeza atapeza Celgene kwa $74 biliyoni mu 2019.

(10) Abecma

Kampani: Co-yopangidwa ndi Bristol-Myers Squibb (BMS) ndi bluebird bio.

Nthawi yogulitsa: Kuvomerezedwa ndi FDA mu Marichi 2021.

Myeloma yobwerera m'mbuyo kapena refractory angapo.

Ndemanga: Abecma ndi lentivirus-based in vitro gene therapy, mankhwala oyamba padziko lonse lapansi a CAR-T olunjika ku BCMA, komanso chithandizo chachisanu cha CAR-T chovomerezedwa ndi FDA.Mfundo ya mankhwala ndi kufotokozera chimeric BCMA cholandirira pa maselo autologous T odwala kudzera lentivirus-mediated chibadwa kusinthidwa mu m'galasi.Pamaso kulowetsedwa kwa selo jini mankhwala, wodwalayo analandira awiri mankhwala a cyclophosphamide ndi fludarabine chisanadze mankhwala.Chithandizo chochotsa ma cell osasinthika a T kuchokera kwa wodwalayo, ndikulowetsanso maselo a T osinthidwa m'thupi la wodwalayo kuti afufuze ndi kupha maselo a khansa omwe akuwonetsa BCMA.

(11) Libmeldy

Kampani: Yopangidwa ndi Orchard Therapeutics.

Nthawi Yogulitsa: Yovomerezedwa ndi European Union kuti ilembedwe mu Disembala 2020.

Zochizira metachromatic leukodystrophy (MLD).

Ndemanga: Libmeldy ndi chithandizo cha majini chozikidwa pa kusintha kwa jini ya lentiviral in vitro ya autologous CD34+ cell.Deta yachipatala ikuwonetsa kuti kulowetsedwa kwa mtsempha umodzi wa Libmeldy ndikothandiza pakusintha koyambirira kwa MLD komanso kuwonongeka kwakukulu kwa magalimoto ndi chidziwitso kwa odwala omwe sanalandire chithandizo azaka zomwezo.

(12) Benoda

Kampani: Yopangidwa ndi WuXi Junuo.

Nthawi yogulitsa: Yavomerezedwa ndi NMPA mu Seputembara 2021.

Zizindikiro: Chithandizo cha B-cell lymphoma (r / r LBCL) yobwereranso kapena yowonongeka kwa odwala akuluakulu pambuyo pa mzere wachiwiri kapena mankhwala ambiri.

Ndemanga: Benoda ndi anti-CD19 CAR-T gene therapy, komanso ndi chida chachikulu cha WuXi Junuo.Ndi chinthu chachiwiri cha CAR-T chovomerezedwa ku China, kupatulapo B-cell lymphoma yobwereranso/refractory.Kuphatikiza apo, WuXi Junuo akufunanso kupanga jakisoni wa Ruiki Orenza wochizira zisonyezo zina zosiyanasiyana, kuphatikiza follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), mzere wachiwiri wofalitsa B-cell lymphoma (DLBCL) ndi acute lymphoblastic leukemia (ALL).

(13) CARVYKTI

Kampani: Chogulitsa choyamba cha Legend Bio.

Nthawi yogulitsa: Kuvomerezedwa ndi FDA mu February 2022.

Chithandizo cha kubwereranso kapena refractory angapo myeloma (R/R MM).

Ndemanga: CARVYKTI (ciltacabtagene autoleucel, yotchedwa Cilta-cel) ndi CAR-T cell immune gene therapy yokhala ndi ma antibodies awiri a domain single omwe akulunjika ku B cell maturation antigen (BCMA).Deta imasonyeza kuti CARVYKTI inasonyeza chiwerengero cha kuyankha kwa 98% mwa odwala omwe ali ndi myeloma yobwereranso kapena yotsutsa omwe adalandira chithandizo chamankhwala anayi kapena kuposerapo, kuphatikizapo proteasome inhibitors, immunomodulators, ndi anti-CD38 monoclonal antibodies.

2. Mu vivo gene therapy yotengera ma vector a virus

(1) Gendicine/kubadwanso mwatsopano

Kampani: Yopangidwa ndi Shenzhen Saibainuo Company.

Nthawi Yogulitsa: Adavomerezedwa kuti alembetse ku China mu 2003.

Zochizira squamous cell carcinoma mutu ndi khosi.

Ndemanga: Recombinant human p53 adenovirus jakisoni Gendicine/Jinshengsheng ndi mankhwala a adenovirus vector gene therapy omwe ali ndi ufulu wodziyimira pawokha waluso la kampani ya Shenzhen Saibainuo.The mankhwala wapangidwa yachibadwa munthu chotupa suppressor jini p53 ndi yokumba kusinthidwa recombinant kugawanika-opereŵera Human adenovirus mtundu 5 wapangidwa anthu adenovirus mtundu 5. Yoyamba ndi yaikulu dongosolo la mankhwala kusonyeza odana ndi chotupa kwenikweni, ndipo chotsirizira makamaka amachita monga chonyamulira.Vector ya adenovirus imanyamula jini yochizira p53 kulowa mu cell yomwe mukufuna, ndikuwonetsa chotupa chopondereza jini p53 mu cell yomwe mukufuna.Chogulitsacho chimatha kuwongolera majini osiyanasiyana odana ndi khansa ndikuwongolera zochitika zamitundu yosiyanasiyana ya oncogene, potero kumakulitsa mphamvu ya anti-chotupa m'thupi ndikukwaniritsa cholinga chopha zotupa.

(2) Mwadzidzidzi

Kampani: Yopangidwa ndi kampani yaku Latvia Latima.

Nthawi yopita kumsika: Inavomerezedwa ku Latvia mu 2004.

Zochizira melanoma.

Ndemanga: Rigvir ndi mankhwala a jini otengera gene-modified ECHO-7 enterovirus vector, yomwe yakhala ikugwiritsidwa ntchito ku Latvia, Estonia, Poland, Armenia, Belarus ndi malo ena, ndipo ikulembetsedwanso ndi EMA ya European Union..Milandu yachipatala m'zaka khumi zapitazi yatsimikizira kuti kachilombo ka Rigvir oncolytic ndi kotetezeka komanso kothandiza, ndipo kumatha kusintha kupulumuka kwa odwala a melanoma ndi nthawi 4-6.Kuphatikiza apo, mankhwalawa ndi oyeneranso mitundu yosiyanasiyana ya khansa, kuphatikiza khansa ya colorectal, khansa ya kapamba, khansa ya chikhodzodzo.khansa, khansa ya impso, khansa ya prostate, khansa ya m'mapapo, khansa ya uterine, lymphosarcoma, ndi zina zotero.

(3) Oncorine/Ankerui

Kampani: Yopangidwa ndi Shanghai Sunway Biotechnology Co., Ltd.

Nthawi Yogulitsa: Zavomerezedwa kuti zilembedwe ku China mu 2005.

Chithandizo cha mutu ndi khosi zotupa, khansa ya chiwindi, kapamba khansa, khomo pachibelekeropo khansa ndi zina khansa.

Ndemanga: Oncorine ndi mankhwala a oncolytic virus gene therapy pogwiritsa ntchito adenovirus ngati vekitala.The oncolytic adenovirus yomwe idapezeka imatha kubwereza makamaka m'matumbo omwe alibe kapena osowa p53 jini, kupangitsa chotupa cell lysis, potero kupha ma cell chotupa.popanda kuwononga maselo abwinobwino.Zotsatira zachipatala zikuwonetsa kuti Anke Rui ali ndi chitetezo chabwino komanso chothandiza pamatenda osiyanasiyana owopsa.

(4) Glybera

Kampani: Yopangidwa ndi UniQure.

Nthawi Yogulitsa: Kuvomerezedwa ku Europe mu 2012.

Zizindikiro: Chithandizo cha kusowa kwa lipoprotein lipase (LPLD) komwe kumakhala kowopsa kapena kobwerezabwereza kwa kapamba ngakhale kudya zakudya zamafuta ochepa.

Ndemanga: Glybera (alipogene tiparvovec) ndi mankhwala ochizira jini otengera AAV ngati vekitala.Mankhwalawa amagwiritsa ntchito AAV monga vekitala kuti asamutsire jini yochizira LPL m'maselo a minofu, kotero kuti maselo ogwirizana amatha kupanga kuchuluka kwa lipoprotein lipase, Imathandiza kuthetsa matenda, ndipo mankhwalawa ndi othandiza kwa nthawi yaitali pambuyo pa ulamuliro umodzi (zotsatira zake zimatha zaka zambiri).Mankhwalawa adachotsedwa m'chaka cha 2017, ndipo zifukwa zomwe adachotsera zitha kukhala zokhudzana ndi zinthu ziwiri: mitengo yamtengo wapatali komanso kufunikira kochepa kwa msika.Mtengo wapakati pa chithandizo chimodzi cha mankhwalawa ndi okwera kwambiri mpaka 1 miliyoni US dollars, ndipo wodwala m'modzi yekha ndiye adagula ndikugwiritsa ntchito mpaka pano.Ngakhale kampani ya inshuwaransi yachipatala idabweza ndalama zokwana madola 900,000 aku US, ndizovuta kwambiri kwa kampani ya inshuwaransi.Kuonjezera apo, chisonyezero cha mankhwalawa ndi chosowa kwambiri, ndi chiwerengero cha pafupifupi 1 mu 1 miliyoni komanso chiwerengero chachikulu cha matenda olakwika.

(5) Imlygic

Kampani: Yopangidwa ndi Amgen.

Nthawi yogulitsa: Mu 2015, idavomerezedwa kuti ilembedwe ku United States ndi European Union.

Zizindikiro: Chithandizo cha zotupa za melanoma zomwe sizingachotsedwe kwathunthu ndi opaleshoni.

Ndemanga: Imlygic ndi jini yosinthidwa (kuchotsa zidutswa zake za jini za ICP34.5 ndi ICP47, ndikuyika jini ya granulocyte-macrophage colony-stimulating factor GM-CSF mu kachilomboka) yochepetsera kachilombo ka herpes simplex mtundu 1 (HSV-1) oncolytic virus, woyamba FDA-approve virus.Njira yoyendetsera ndi jekeseni wa intralesional.Jekeseni mwachindunji mu zotupa za melanoma zingayambitse kuphulika kwa maselo a chotupa ndikutulutsa ma antigen opangidwa ndi chotupa ndi GM-CSF kulimbikitsa mayankho odana ndi chotupa.

(6) Luxturna

Kampani: Yopangidwa ndi Spark Therapeutics, kampani ya Roche.

Nthawi yogulitsa: Yovomerezedwa ndi FDA mu 2017, kenako idavomerezedwa kuti igulidwe ku Europe mu 2018.

Zochizira ana ndi akulu ndi masomphenya imfa chifukwa masinthidwe mu iwiri buku la RPE65 jini koma ndi chiwerengero chokwanira yotheka retina maselo.

Ndemanga: Luxturna ndi mtundu wa AAV-based gene therapy womwe umayendetsedwa ndi jakisoni wa subretinal.The gene therapy imagwiritsa ntchito AAV2 monga chonyamulira kuti adziwitse kopi yogwira ntchito ya jini yachibadwa ya RPE65 m'maselo a retina a wodwalayo, kotero kuti maselo ogwirizanawo afotokoze mapuloteni abwino a RPE65 kuti athe kubwezera chilema cha mapuloteni a RPE65 a wodwalayo, motero amawongolera masomphenya a wodwalayo.

(7) Zolgensma

Kampani: Yopangidwa ndi AveXis, wothandizira wa Novartis.

Nthawi yogulitsa: Yovomerezedwa ndi FDA mu Meyi 2019.

Chithandizo cha spinal muscular atrophy (Spinal Muscular Atrophy, SMA) odwala osakwana zaka ziwiri.

Ndemanga: Zolgensma ndi chithandizo cha majini chotengera AAV vector.Mankhwalawa ndi njira yokhayo yothandizira nthawi imodzi ya spinal muscular atrophy yovomerezeka kuti igulitsidwe padziko lonse lapansi.tsamba, ndikupita patsogolo.Chithandizo cha majinichi chimagwiritsa ntchito vekitala ya scAAV9 kuti iwonetsere jini yabwinobwino ya SMN1 mwa odwala kudzera m'mitsempha, kupanga mapuloteni abwinobwino a SMN1, potero kumathandizira magwiridwe antchito a maselo okhudzidwa monga ma neuroni agalimoto.Mosiyana ndi zimenezi, mankhwala a SMA Spinraza ndi Evrysdi amafuna kubwereza mobwerezabwereza kwa nthawi yaitali, ndi Spinraza yomwe imaperekedwa ngati jekeseni ya msana miyezi inayi iliyonse, ndi Evrysdi, mankhwala a pakamwa tsiku ndi tsiku.

(8) Kusokonezeka

Kampani: Yopangidwa ndi Daiichi Sankyo Company Limited (TYO: 4568).

Nthawi yopita kumsika: Chivomerezo chovomerezeka kuchokera ku Unduna wa Zaumoyo, Ntchito ndi Umoyo ku Japan (MHLW) mu Juni 2021.

Zochizira malignant glioma.

Ndemanga: Delytact ndi chinthu chachinayi cha oncolytic virus gene therapy chovomerezeka padziko lonse lapansi komanso chida choyamba cha virus cha oncolytic chovomerezeka kuchiza glioma yoyipa.Delytact ndi kachilombo ka herpes simplex virus mtundu 1 (HSV-1) oncolytic yopangidwa ndi Dr. Todo ndi anzake.Delytact imayambitsa kusintha kwina kochotsa mu G207 genome ya m'badwo wachiwiri wa HSV-1, kupititsa patsogolo kusinthika kwake kosankha m'maselo a khansa komanso kulowetsedwa kwa mayankho a anti-chotupa, ndikusunga chitetezo chambiri.Delytact ndiye m'badwo woyamba wachitatu wa oncolytic HSV-1 pano pakuwunika kwachipatala.Kuvomerezedwa kwa Delytact ku Japan kudachokera ku kuyesa kwachipatala kwa gawo lachiwiri la mkono umodzi.Odwala omwe ali ndi glioblastoma yobwerezabwereza, Delytact anakumana ndi mapeto oyambirira a kupulumuka kwa chaka chimodzi, ndipo zotsatira zake zimasonyeza kuti Delytact inachita bwino kuposa G207.Kubwereza mwamphamvu komanso ntchito yayikulu ya antitumor.Izi ndizothandiza mumitundu yolimba yotupa kuphatikiza bere, prostate, schwannoma, nasopharyngeal, hepatocellular, colorectal, zotupa zotumphukira zamitsempha zam'mitsempha ndi khansa ya chithokomiro.

(9) Zosangalatsa

Kampani: Yopangidwa ndi PTC Therapeutics, Inc. (NASDAQ: PTCT).

Nthawi yogulitsa: Kuvomerezedwa ndi EU mu Julayi 2022.

Chizindikiro: Pakuchepa kwa L-amino acid decarboxylase (AADC) wonunkhira, wovomerezeka kuti azichiza odwala omwe ali ndi miyezi 18 kapena kuposerapo.

Ndemanga: Upstaza™ (eladocagene exuparvovec) ndi mu vivo gene therapy pogwiritsa ntchito adeno-associated virus type 2 (AAV2) ngati vector.Wodwalayo amadwala chifukwa cha kusintha kwa jini yomwe imayika enzyme ya AADC.AAV2 imakhala ndi jini yathanzi yolemba enzyme ya AADC.The achire zotsatira zimatheka mu mawonekedwe a chibadwa chipukuta misozi.Mwachidziwitso, mlingo umodzi ndi wothandiza kwa nthawi yaitali.Ndi njira yoyamba yogulitsira majini yomwe imalowetsedwa mwachindunji muubongo.Chilolezo cha malonda chimagwira ntchito ku mayiko onse 27 a EU, komanso Iceland, Norway ndi Liechtenstein.

(9) Roctavian

Kampani: Yopangidwa ndi BioMarin Pharmaceutical (BioMarin).

Nthawi Yogulitsa: Kuvomerezedwa ndi EU mu Ogasiti 2022.

Zochizira wamkulu odwala kwambiri hemophilia A popanda mbiri FVIII chinthu chopinga ndi AAV5 antibody zoipa.

Ndemanga: Roctavian (valoctocogene roxaparvovec) amagwiritsa ntchito AAV5 ngati ivekita ndipo amagwiritsa ntchito cholimbikitsa chiwindi chamunthu cha HLP kuyendetsa mawu a human coagulation factor eight (FVIII) pomwe domain B yachotsedwa.Lingaliro la European Commission kuti livomereze kugulitsidwa kwa valoctocogene roxaparvovec likutengera zonse za pulogalamu yachitukuko chamankhwala.Pakati pawo, gawo III matenda mayesero GENEr8-1 anasonyeza kuti poyerekeza ndi deta chaka pamaso kulembetsa, pambuyo kulowetsedwa umodzi wa valoctocogene roxaparvovec, Nkhani anali kwambiri m`munsi kwambiri pachaka magazi mlingo (ABR), zochepa kawirikawiri ntchito recombinant factor VIII (F8) kukonzekera mapuloteni, kapena kuwonjezeka kwambiri F8 ntchito m'magazi a thupi.Pambuyo pa masabata a 4 a chithandizo, maphunziro a F8 pachaka ndi ABR omwe amafunikira chithandizo adachepetsedwa ndi 99% ndi 84%, motero, kusiyana kwakukulu (p <0.001).Mbiri yachitetezo inali yabwino, popanda anthu omwe anali ndi F8 factor inhibition, malignancy, kapena thrombotic side effects, ndipo palibe zochitika zazikulu zokhudzana ndi chithandizo (SAEs) zomwe zinanenedwa.

3. Mankhwala ang'onoang'ono a nucleic acid

(1) Vitravene

Kampani: Yopangidwa ndi Ionis Pharma (yemwe kale anali Isis Pharma) ndi Novartis.

Nthawi yogulitsa: Adavomerezedwa ndi FDA ndi EU EMA mu 1998 ndi 1999.

Zochizira cytomegalovirus retinitis odwala HIV.

Ndemanga: Vitravene ndi antisense oligonucleotide mankhwala ndi oligonucleotide yoyamba mankhwala ovomerezeka kuti malonda padziko lonse.Kumayambiriro kwa msika, kufunikira kwa msika kwa mankhwala oletsa anti-cytomegalovirus kunali kofulumira kwambiri;ndiye chifukwa cha chitukuko cha mankhwala ochepetsa mphamvu ya kachilombo ka HIV, chiwerengero cha matenda a cytomegalovirus chinatsika kwambiri.Chifukwa cha kuchepa kwa msika, mankhwalawa adatulutsidwa mu 2002 ndi 2006 Kuchotsa m'mayiko a EU ndi US.

(2) Magulu

Kampani: Co-yopangidwa ndi Pfizer ndi Eyetech.

Nthawi yopita kumsika: Adavomerezedwa kuti alembetse ku United States mu 2004.

Zochizira neovascular zaka zokhudzana macular alibe.

Ndemanga: Macugen ndi pegylated modified oligonucleotide mankhwala omwe amatha kulunjika ndi kumangiriza ku vascular endothelial growth factor (VEGF165 isoform), ndipo imayendetsedwa ndi jekeseni wa intravitreal.

(3) Defitelio

Kampani: Yopangidwa ndi Jazz.

Nthawi yogulitsa: Adavomerezedwa ndi European Union mu 2013, ndikuvomerezedwa ndi FDA mu Marichi 2016.

Zochizira kwa chiwindi venule occlusive matenda kugwirizana ndi aimpso kapena m`mapapo mwanga kukanika pambuyo hematopoietic tsinde cell kupatsidwa zina.

Ndemanga: Defitelio ndi oligonucleotide mankhwala, osakaniza oligonucleotides ndi plasmin katundu.Idachotsedwa mu 2009 pazifukwa zamalonda.

(4) Chinamro

Kampani: Yopangidwa ndi Ionis Pharma ndi Kastle.

Nthawi Yogulitsa: Adavomerezedwa ku United States ngati mankhwala amasiye mu 2013.

Pakuti adjuvant mankhwala a homozygous banja hypercholesterolemia.

Ndemanga: Kynamro ndi antisense oligonucleotide mankhwala, antisense oligonucleotide kulunjika anthu apo B-100 mRNA.Kynamro amaperekedwa ngati 200 mg subcutaneously kamodzi pa sabata.

(5) Spinraza

Kampani: Yopangidwa ndi Ionis Pharmaceuticals.

Nthawi Yogulitsa: Adavomerezedwa ndi FDA mu Disembala 2016.

Zochizira msana minofu atrophy (SMA).

Ndemanga: Spinraza (nusinersen) ndi antisense oligonucleotide mankhwala.Spinraza imatha kusintha kuphatikizika kwa RNA kwa jini ya SMN2 pomanga malo ophatikizira a SMN2 exon 7, potero kukulitsa kupanga kwa protein ya SMN yogwira ntchito mokwanira.Mu Ogasiti 2016, BIOGEN Corporation idagwiritsa ntchito mwayi wawo kupeza ufulu wapadziko lonse wa Spinraza.Spinraza idayamba kuyesa kwachipatala kwa anthu mu 2011. M'zaka 5 zokha, idavomerezedwa ndi FDA mu 2016, kusonyeza kuti FDA ikuzindikira mokwanira za mphamvu zake.Mankhwalawa adavomerezedwa kuti agulitsidwe ku China mu Epulo 2019. Kuzungulira konse kwa kuvomereza kwa Spinraza ku China kuli kosakwana miyezi 6.Patha zaka 2 ndi miyezi 2 kuchokera pomwe Spinraza idavomerezedwa koyamba ku United States.Matenda osowa akunja otere a blockbuster mankhwala atsopano ali Kuthamanga kwa mndandanda ku China kuli kale mwachangu kwambiri.Izi zilinso chifukwa cha "Chidziwitso pa Kutulutsidwa kwa Mndandanda Woyamba wa Mankhwala Atsopano Akunja Omwe Akufunika Mwachangu Pakafukufuku Wachipatala" woperekedwa ndi Center for Drug Evaluation pa Novembara 1, 2018, yomwe idaphatikizidwa mugulu loyamba lamankhwala 40 ofunikira akunja kuti awonedwe mwachangu, ndipo Spinraza adakhala nawo.

(6) Eksodo 51

Kampani: Yopangidwa ndi AVI BioPharma (yemwe inadzatchedwanso Sarepta Therapeutics).

Nthawi Yogulitsa: Adavomerezedwa ndi FDA mu Seputembala 2016.

Zochizira Duchenne muscular dystrophy (DMD) ndi DMD gene mutation mu exon 51 kudumpha jini.

Ndemanga: Exondys 51 ndi antisense oligonucleotide mankhwala.Antisense oligonucleotide imatha kumangirira ku exon 51 malo a pre-mRNA a jini ya DMD, zomwe zimapangitsa kuti pakhale mRNA wokhwima.Excision, potero kukonza pang'ono chimango chowerengera cha mRNA, kumathandiza wodwalayo kupanga mitundu ina ya dystrophin yomwe ndi yaifupi kuposa mapuloteni abwinobwino, potero kuwongolera zizindikiro za wodwalayo.

(7) Tegsedi

Kampani: Yopangidwa ndi Ionis Pharmaceuticals.

Nthawi yopita kumsika: Yavomerezedwa ndi European Union kuti igulitsidwe mu Julayi 2018.

Zochizira hereditary transthyretin amyloidosis (hATTR).

Ndemanga: Tegsedi ndi antisense oligonucleotide mankhwala olunjika transthyretin mRNA.Ndiwo mankhwala oyamba padziko lonse ovomerezeka ochizira HATTR.Njira ya makonzedwe ndi subcutaneous jekeseni.Mankhwalawa amachepetsa kupanga kwa mapuloteni a ATTR poyang'ana mRNA ya transthyretin (ATTR), ndipo ali ndi chiopsezo chabwino cha chiopsezo pochiza ATTR.Palibe gawo la matenda kapena kukhalapo kwa cardiomyopathy kunali kofunikira.

(8) Pamwamba

Kampani: Yopangidwa ndi Alnylam ndi Sanofi.

Nthawi Yogulitsa: Zavomerezedwa kuti zilembedwe ku United States mu 2018.

Zochizira hereditary transthyretin amyloidosis (hATTR).

Ndemanga: Onpattro ndi mankhwala a siRNA omwe amayang'ana transthyretin mRNA, omwe amachepetsa kupanga kwa ATTR mapuloteni m'chiwindi ndi kusonkhanitsa kwa amyloid deposits mu mitsempha yozungulira poyang'ana mRNA ya transthyretin (ATTR)., potero kukonza ndi kuthetsa zizindikiro za matenda.

(9) Givlaari

Kampani: Yopangidwa ndi Alnylam Corporation.

Nthawi yogulitsa: Yovomerezedwa ndi FDA mu Novembala 2019.

Zochizira pachimake kwa chiwindi porphyria (AHP) akuluakulu.

Ndemanga: Givlaari ndi mankhwala a siRNA, mankhwala achiwiri a siRNA ovomerezeka kuti agulitsidwe pambuyo pa Onpattro.Mankhwalawa amaperekedwa pansi pa khungu ndipo amalimbana ndi mRNA kuti awononge mapuloteni a ALAS1.Chithandizo cha mwezi ndi mwezi cha Givlaari chimatha kuchepetsa kwambiri komanso mosalekeza kuchuluka kwa ALAS1 m'chiwindi, potero kumachepetsa milingo ya neurotoxic ALA ndi PBG kufika pamlingo wabwinobwino, potero Kuchepetsa zizindikiro za matenda a wodwalayo.Detayo inasonyeza kuti odwala omwe amathandizidwa ndi Givlaari anali ndi 74% kuchepetsa chiwerengero cha matenda oyaka moto poyerekeza ndi gulu la placebo.

(10) Vyondys53

Kampani: Yopangidwa ndi Sarepta Therapeutics.

Nthawi yogulitsa: Yovomerezedwa ndi FDA mu Disembala 2019.

Chizindikiro: Zochizira odwala a DMD omwe ali ndi dystrophin gene exon 53 splice mutation.

Ndemanga: Vyondys 53 ndi antisense oligonucleotide mankhwala.Mankhwala a oligonucleotide amayang'ana njira yolumikizirana ya dystrophin mRNA precursor.M'njira yosadziwika bwino ya dystrophin mRNA precursor, Exon 53 yakunja idagawika pang'ono, mwachitsanzo, palibe pa mRNA yokhwima, ndipo idapangidwa kuti ipange mapuloteni ocheperako koma osagwira ntchito a dystrophin, potero amathandizira kuchita masewera olimbitsa thupi kwa odwala.

(11) Waylivra

Kampani: Yopangidwa ndi Ionis Pharmaceuticals ndi othandizira ake Akcea Therapeutics.

Nthawi Yogulitsa: Yavomerezedwa ndi European Medicines Agency (EMA) mu Meyi 2019.

Chizindikiro: Monga chithandizo chothandizira pazakudya zolamulidwa mwa odwala akuluakulu omwe ali ndi matenda amtundu wa chylomicronemia (FCS).

Ndemanga: Waylivra ndi mankhwala a antisense oligonucleotide, omwe ndi mankhwala oyamba omwe amavomerezedwa kuti azichiza FCS padziko lapansi.

(12) Levi

Kampani: Yopangidwa ndi Novartis.

Nthawi Yogulitsa: Kuvomerezedwa ndi EU mu Disembala 2020.

Zochizira wamkulu wamkulu hypercholesterolemia (heterozygous banja ndi sanali banja) kapena wosanganiza dyslipidemia.

Ndemanga: Leqvio ndi mankhwala a siRNA omwe akulunjika ku PCSK9 mRNA.Ndi mankhwala oyamba padziko lonse otsitsa cholesterol (LDL-C) siRNA.Njira ya makonzedwe ndi subcutaneous jekeseni.Mankhwalawa amagwira ntchito ndi kusokoneza kwa RNA kuti achepetse mapuloteni a PCSK9, omwe amachepetsanso LDL-C.Zambiri zachipatala zikuwonetsa kuti Leqvio amatha kuchepetsa LDL-C pafupifupi 50% mwa odwala omwe milingo ya LDL-C singathe kuchepetsedwa mpaka mulingo womwe mukufuna ngakhale kuti ma statins amalekerera kwambiri.

(13) Okalamba

Kampani: Yopangidwa ndi Alnylam Pharmaceuticals.

Nthawi Yogulitsa: Kuvomerezedwa ndi EU mu Novembala 2020.

Zochizira chachikulu hyperoxaluria mtundu 1 (PH1).

Ndemanga: Oxlumo ndi mankhwala a siRNA omwe akulunjika ku hydroxy acid oxidase 1 (HAO1) ​​mRNA, yomwe imayendetsedwa pansi pa khungu.The mankhwala anayamba ntchito Alnylam atsopano kumatheka kukhazikika mankhwala ESC-GalNAc conjugation luso, amene amathandiza subcutaneously kutumikiridwa siRNAs ndi kulimbikira kwambiri ndi lapamwamba.Mankhwalawa amalimbana ndi kuwonongeka kapena kulepheretsa kwa hydroxy acid oxidase 1 (HAO1) ​​mRNA, amachepetsa mlingo wa glycolate oxidase m'chiwindi, ndiyeno amadya gawo lapansi lofunikira kuti apange oxalate ndi kuchepetsa kupanga oxalate kuti athe kuchepetsa matenda ndi kusintha zizindikiro za matenda kwa odwala.

(14) Viltepso

Company: Yopangidwa ndi NS Pharma, subsidiary ya Nippon Shinyaku.

Nthawi yogulitsa: Yovomerezedwa ndi FDA mu Ogasiti 2020.

Zochizira Duchenne muscular dystrophy (DMD) ndi DMD gene mutation mu exon 53 kudumpha jini.

Ndemanga: Viltepso ndi phosphorodiamide morpholino oligonucleotide mankhwala.Mankhwala a oligonucleotide amatha kumangirira ku exon 53 malo a pre-mRNA a jini ya DMD, zomwe zimapangitsa kupanga mRNA wokhwima.Exon imachotsedwa pang'ono, motero imawongolera pang'ono mawonekedwe a mRNA, kuthandiza wodwalayo kupanga mitundu ina ya dystrophin yomwe ndi yaifupi kuposa mapuloteni abwinobwino, potero kuwongolera zizindikiro za wodwalayo.

(15) Amvuttra (vutrisiran)

Kampani: Yopangidwa ndi Alnylam Pharmaceuticals.

Nthawi yogulitsa: Kuvomerezedwa ndi FDA mu June 2022.

Zochizira wamkulu cholowa transthyretin amyloidosis ndi polyneuropathy (hATTR-PN).

Ndemanga: Amvuttra (Vutrisiran) ndi mankhwala a siRNA omwe akulunjika ku transthyretin (ATTR) mRNA, yomwe imayendetsedwa ndi jakisoni wa subcutaneous.Vutrisiran idapangidwa kutengera Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc yolumikizana yoperekera nsanja yokhala ndi mphamvu komanso kukhazikika kwa metabolic.Chivomerezo cha mankhwalawa chimachokera ku deta ya miyezi ya 9 kuchokera ku kafukufuku wake wachipatala wa Phase III (HELIOS-A), zomwe zotsatira zake zikuwonetsa kuti mankhwalawa adawongolera zizindikiro za hATTR-PN, ndi odwala oposa 50% akubwerera kapena kusiya kupita patsogolo.

4. Mankhwala ena ochizira majini

(1) Rexin-G

Kampani: Yopangidwa ndi Epeius Biotech.

Nthawi Yogulitsa: Yavomerezedwa ndi Philippine Food and Drug Administration (BFAD) mu 2005.

Zizindikiro: Zochizira makhansa apamwamba omwe samva chemotherapy.

Ndemanga: Rexin-G ndi jakisoni wodzaza jini wa nanoparticle.Imayambitsa jini yosinthika ya cyclin G1 m'maselo omwe mukufuna kudzera pa retroviral vector kuti aphe makamaka zotupa zolimba.Njira makonzedwe ndi mtsempha wa magazi kulowetsedwa.Monga chotupa cholimbana ndi mankhwala omwe amafunafuna mwachangu ndikuwononga maselo a khansa ya metastatic, amakhala ndi zotsatirapo zake kwa odwala omwe sagwira ntchito motsutsana ndi mankhwala ena a khansa, kuphatikiza biologics yomwe imayang'aniridwa.

(2) Neovasculgen

Kampani: Yopangidwa ndi Human stem cell Institute.

Nthawi yolembedwa: Anavomerezedwa kuti alembetse ku Russia pa December 7, 2011, kenako analembedwa ku Ukraine mu 2013.

Zochizira zotumphukira mtsempha wamagazi matenda, kuphatikizapo kwambiri nthambi ischemia.

Ndemanga: Neovasculgen ndi DNA plasmid-based gene therapy yomwe jini ya vascular endothelial growth factor (VEGF) 165 imapangidwira pamsana wa plasmid ndikulowetsedwa mwa odwala.

(3) Collategene

Company: Co-yopangidwa ndi Osaka University ndi venture capital firms.

Nthawi yolembetsa: Yovomerezedwa ndi Unduna wa Zaumoyo, Ntchito ndi Ubwino ku Japan kuti ilembedwe mu Ogasiti 2019.

Chithandizo cha kwambiri m`munsi malekezero ischemia.

Ndemanga: Collategene ndi plasmid-based gene therapy, mankhwala oyamba amtundu waku Japan opangidwa ndi AnGes.Chigawo chachikulu cha mankhwalawa ndi plasmid wamaliseche yomwe ili ndi mndandanda wa jini wa human hepatocyte growth factor (HGF).Ngati mankhwala jekeseni mu minofu ya m`munsi miyendo, anasonyeza HGF kulimbikitsa mapangidwe atsopano mitsempha ya magazi kuzungulira occluded mitsempha.Mayesero azachipatala atsimikizira mphamvu zake pakuwongolera zilonda.

TSIRIZA