N'oge na-adịbeghị anya, a kwadoro ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nketa atọ maka ịzụ ahịa, ya bụ: (1) Na Julaị 21, 2022, PTC Therapeutics, Inc. (NASDAQ: PTCT) kwupụtara na European Commission kwadoro usoro ọgwụgwọ AAV ya Upstaza ™ Ọ bụ usoro ọgwụgwọ mkpụrụ ndụ mbụ a na-ere ozugbo etinyere ya ozugbo n'ime ụbụrụ (lee isiokwu gara aga n'ime ụbụrụ ụbụrụ mbụ' The MilepyAA). kwadoro maka ịzụ ahịa).(2) Na August 17, 2022, US Food and Drug Administration (FDA) kwadoro usoro ọgwụgwọ mkpụrụ ndụ Bluebird Bio nke Zynteglo (betibeglogene autotemcel, beti-cel) maka ọgwụgwọ beta thalassemia.Nkwenye nke ọgwụgwọ na United States bụ ihe ịrụ ụka adịghị ya na ọ bụ "enyemaka na snow" maka Bluebird Bio, nke nọ na nsogbu ego.(3) Na August 24, 2022, BioMarin Pharmaceutical (BioMarin) kwupụtara na European Commission kwadoro ahịa ahịa nke ROCTAVIAN ™ (valoctocogene roxaparvovec), usoro ọgwụgwọ mkpụrụ ndụ maka hemophilia A, maka ọgwụgwọ nke ndị ọrịa na-enweghị akụkọ ihe mere eme nke FVIII Factor inhibitors na ndị ọrịa AAV5 na-adịghị mma nwere ọrịa hemophilia na-adịghị mma. philia A genetherapy kwadoro maka ire ahịa).Ka ọ dị ugbu a, a kwadoro ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nketa iri anọ na otu maka ịzụ ahịa n'ụwa niile.

Gene bụ ngalaba mkpụrụ ndụ ihe nketa na-achịkwa àgwà.Ewezuga mkpụrụ ndụ ihe nketa nke ụfọdụ nje, bụ́ ndị mejupụtara RNA, mkpụrụ ndụ ihe nketa nke ihe ka ọtụtụ n’ime ihe ndị mejupụtara ya bụ DNA.Ọtụtụ ọrịa nke akụkụ ahụ na-ebute site na mmekọrịta dị n'etiti mkpụrụ ndụ ihe nketa na gburugburu ebe obibi, na ọtụtụ ọrịa nwere ike ịgwọ ma ọ bụ belata n'ezie site na ọgwụgwọ mkpụrụ ndụ ihe nketa.A na-ahụta ọgwụgwọ mkpụrụ ndụ ka ọ bụrụ mgbanwe n'ọhịa ọgwụ na ụlọ ahịa ọgwụ.Usoro ọgwụgwọ mkpụrụ ndụ sara mbara gụnyere ọgwụ ndị dabere na ọgwụ DNA megharịrị DNA (dị ka viral vector dabeere na vivo gene therapy ọgwụ, in vitro gene therapy ọgwụ, plasmid ọgwụ gba ọtọ, wdg) na RNA ọgwụ (dị ka antisense oligonucleotide ọgwụ, siRNA ọgwụ, na mRNA gene therapy, wdg);Ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nketa akọwapụtara nke ọma gụnyere ọgwụ plasmid DNA, ọgwụ ọgwụgwọ mkpụrụ ndụ sitere na vectors viral, ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nke sitere na vectors nje, usoro ndezi mkpụrụ ndụ ihe nketa na ọgwụ ọgwụgwọ mkpụrụ ndụ na-agbanwe mkpụrụ ndụ ihe nketa na vitro.Ka ọtụtụ afọ nke mmepe siri ike gasịrị, ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nketa enwetala nsonaazụ na-akpali akpali.(ewezuga ọgwụ mgbochi DNA na ọgwụ mgbochi mRNA), akwadoro ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nketa 41 maka ịre ahịa n'ụwa.Site na mmalite nke ngwaahịa na mmepe ngwa ngwa nke teknụzụ ọgwụgwọ mkpụrụ ndụ ihe nketa, usoro ọgwụgwọ mkpụrụ ndụ ihe nketa na-achọ iweta oge mmepe ngwa ngwa.

Nhazi ọgwụgwọ mkpụrụ ndụ ihe nketa (isi mmalite foto: Biological Jingwei)

Edemede a depụtara usoro ọgwụgwọ mkpụrụ ndụ iri anọ na otu akwadoro maka ịre ahịa (ewezuga ọgwụ mgbochi DNA na ọgwụ mRNA).

1. In vitro gene therapy

(1) Strimvelis

Ụlọ ọrụ: GlaxoSmithKline (GSK) mebere ya.

Oge ịre ahịa: European Union kwadoro na Mee 2016.

Ngosipụta: Maka ọgwụgwọ nke nnukwu mkpokọta immunodeficiency (SCID).

Nkwuwa: Usoro usoro ọgwụgwọ a n'ozuzu bụ ibu ụzọ nweta mkpụrụ ndụ hematopoietic nke onye ọrịa, gbasaa ma mebe ha na vitro, wee jiri retrovirus webata otu mkpụrụ ndụ ADA (adenosine deaminase) na-arụ ọrụ n'ime mkpụrụ ndụ hematopoietic ha, n'ikpeazụkwa nyefe mkpụrụ ndụ hematopoietic gbanwetụrụ.A na-agbanyeghachi mkpụrụ ndụ hematopoietic n'ime ahụ.Nsonaazụ ụlọ ọgwụ gosiri na afọ 3 dị ndụ ndụ nke ndị ọrịa ADA-SCID ejiri Strimvelis gwọọ bụ 100%.

(2) Zalmoxis

Ụlọ ọrụ: MolMed, Italy mepụtara.

Oge ịre ahịa: Nweta ikike ịre ahịa ọnọdụ EU na 2016.

Ngosipụta: A na-eji ya maka ọgwụgwọ adjuvant nke usoro ahụ ji alụso ọrịa ọgụ mgbe a gbasasịrị mkpụrụ ndụ hematopoietic stem cell.

Okwu: Zalmoxis bụ ihe allogeneic T cell igbu onwe mkpụrụ ndụ immunotherapy meziri site retroviral vector.Mkpụrụ ndụ igbu onwe 1NGFR na HSV-TK Mut2 na-enye ndị mmadụ ohere iji ganciclovir n'oge ọ bụla iji gbuo mkpụrụ ndụ T nke na-akpata mmeghachi omume na-adịghị mma, gbochie mmebi ọzọ nke GVHD nke nwere ike ime, ma weghachite ọrụ mgbochi na ndị ọrịa nwere HSCT haploidentical mgbe ịwa ahụ Escort.

(3) Invossa-K

Ụlọ ọrụ: Ụlọ ọrụ TissueGene (KolonTissueGene) mepụtara.

Oge ịre ahịa: Ekwenyere maka ndepụta na South Korea na Julaị 2017.

Ngosipụta: Maka ọgwụgwọ ọrịa ogbu na nkwonkwo degenerative ikpere.

Nkọwa: Invossa-K bụ usoro ọgwụgwọ mkpụrụ ndụ ihe nketa allogeneic metụtara chondrocytes mmadụ.A na-agbanwe mkpụrụ ndụ Alogeneic na mkpụrụ ndụ ihe nketa na vitro, mkpụrụ ndụ ndị a gbanwere nwere ike igosipụta ma zoo ihe na-agbanwe uto β1 (TGF-β1) mgbe ịgba ọgwụ mgbochi intra-articular gasịrị.β1), si otú ahụ na-emeziwanye ihe mgbaàmà nke ọrịa ogbu na nkwonkwo.Nsonaazụ ụlọ ọgwụ na-egosi na Invossa-K nwere ike melite ogbu na nkwonkwo ikpere.Ndị na-ahụ maka ọgwụ South Korea kagburu ikike ahụ n'afọ 2019 n'ihi na onye nrụpụta ahụ debara aha na-ezighi ezi ihe eji eme ya.

(4) Zynteglo

Ụlọ ọrụ: Ụlọ ọrụ American bluebird bio (bluebird bio) mepụtara.

Oge ịre ahịa: European Union kwadoro na 2019, yana FDA kwadoro na August 2022.

Ngosipụta: Maka ọgwụgwọ β-thalassemia na-adabere na mmịnye ọbara.

Nkwuputa: Zynteglo bụ ọgwụ lentiviral in vitro gene therapy, nke na-eji vector lentiviral webata nnomi na-arụ ọrụ nke mkpụrụ ndụ β-globin nkịtị (βA-T87Q-globin gene) n'ime mkpụrụ ndụ hematopoietic na-ewepụ n'aka ndị ọrịa., wee nyeghachi mkpụrụ ndụ sel hematopoietic autologous autologous n'ime onye ọrịa.Ozugbo onye ọrịa nwere mkpụrụ ndụ βA-T87Q-globin nkịtị, ha nwere ike imepụta protein HbAT87Q nkịtị, nke nwere ike belata nke ọma ma ọ bụ wepụ mkpa mmịnye ọbara.Ọ bụ ọgwụgwọ otu oge e mere iji dochie mmịnye ọbara ogologo ndụ na ọgwụ ndị na-adịru ogologo ndụ maka ndị ọrịa gbara afọ 12 gbagowe.

(5) Skysona

Ụlọ ọrụ: Ụlọ ọrụ American bluebird bio (bluebird bio) mepụtara.

Oge ịre ahịa: Ndị EU kwadoro maka ịre ahịa na Julaị 2021.

Ngosipụta: Maka ọgwụgwọ nke mmalite ụbụrụ adrenoleukodystrophy (CALD).

Okwu: Skysona gene therapy bụ naanị otu oge usoro ọgwụgwọ mkpụrụ ndụ ihe nke akwadoro maka ọgwụgwọ nke ụbụrụ adrenoleukodystrophy mmalite (CALD).Skysona (elivaldogene autotemcel, Lenti-D) bụ hematopoietic stem cell lentiviral in vitro gene therapy Lenti-D.Usoro ọgwụgwọ n'ozuzu nke usoro ọgwụgwọ bụ nke a: a na-ewepụ mkpụrụ ndụ hematopoietic autologous n'aka onye ọrịa, gbanwee in vitro site na lentivirus na-ebu mkpụrụ ndụ ABCD1 mmadụ, wee tinyeghachi ya n'ime onye ọrịa.Maka ọgwụgwọ nke ndị ọrịa nọ n'okpuru afọ 18 nwere mutation ABCD1 na CALD.

(6) Kymriah

Ụlọ ọrụ: Novartis mepụtara.

Oge ịre ahịa: FDA kwadoro na August 2017.

Ngosipụta: Ọgwụgwọ nke precursor B-cell nnukwu lymphoblastic leukemia (ALL) na nlọghachite na refractory DLBCL.

Nkọwa: Kymriah bụ ọgwụ lentiviral in vitro gene therapy, usoro ọgwụgwọ CAR-T nke mbụ nke ụwa kwadoro, na-ezubere CD19 na iji ihe na-emekọ ihe ọnụ 4-1BB.Ọnụahịa bụ $475,000 na US na $313,000 na Japan.

(7)Yescarta

Ụlọ ọrụ: Kite Pharma, onye enyemaka nke Gilead mepụtara.

Oge ịre ahịa: FDA kwadoro na Ọktoba 2017.

Ngosipụta: Maka ọgwụgwọ nke nlọghachi azụ ma ọ bụ refractory nnukwu B-cell lymphoma.

Azịza: Yescarta bụ usoro ọgwụgwọ retroviral in vitro gene therapy.Ọ bụ ọgwụgwọ CAR-T nke abụọ akwadoro n'ụwa.Ọ na-elekwasị anya CD19 na-eji ihe costimulatory nke CD28.Ọnụahịa na US bụ $ 373,000.

(8) Tecartus

Ụlọ ọrụ: Gilead (GILD) mebere ya.

Oge ịre ahịa: FDA kwadoro na Julaị 2020.

Ngosipụta: Maka nlọghachite ma ọ bụ refractory mantle cell lymphoma.

Okwu: Tecartus bụ usoro ọgwụgwọ cell CAR-T nke na-achọ CD19, ma bụrụ usoro ọgwụgwọ CAR-T nke atọ akwadoro maka ire ahịa n'ụwa.

(9) Breyanzi

Ụlọ ọrụ: Bristol-Myers Squibb (BMS) mepụtara.

Oge ịre ahịa: FDA kwadoro na February 2021.

Ngosipụta: Nlaghachi ma ọ bụ refractory (R/R) nnukwu lymphoma B-cell (LBCL).

Nkwupụta: Breyanzi bụ ọgwụgwọ mkpụrụ ndụ in vitro dabere na lentivirus, yana ọgwụgwọ CAR-T nke anọ akwadoro maka ịre ahịa n'ụwa, na-ezubere CD19.Nkwenye nke Breyanzi bụ ihe dị ịrịba ama maka Bristol-Myers Squibb na ngalaba immunotherapy cellular, nke Bristol-Myers nwetara mgbe ọ nwetara Celgene maka ijeri $ 74 na 2019.

(10) Abecma

Ụlọ ọrụ: Ụlọ ọrụ-mepụtara site na Bristol-Myers Squibb (BMS) na bluebird bio.

Oge ịre ahịa: FDA kwadoro na Machị 2021.

Ngosipụta: ọtụtụ myeloma na-alaghachi azụ ma ọ bụ na-emegharị ahụ.

Okwu: Abecma bụ lentivirus dabere na vitro gene therapy, usoro ọgwụgwọ mkpụrụ ndụ CAR-T mbụ nke ụwa na-ezubere BCMA, yana ọgwụgwọ CAR-T nke ise nke FDA kwadoro.Ụkpụrụ ọgwụ bụ igosipụta chimeric BCMA nnata na mkpụrụ ndụ T autologous nke onye ọrịa site na mgbanwe mkpụrụ ndụ ihe nketa lentivirus na vitro.Tupu infusion nke mkpụrụ ndụ mkpụrụ ndụ mkpụrụ ndụ, onye ọrịa natara ogige abụọ nke cyclophosphamide na fludarabine maka ọgwụgwọ mbụ.Ọgwụgwọ iji wepụ mkpụrụ ndụ T na-adịghị agbanwe agbanwe n'aka onye ọrịa, wee tinyeghachi mkpụrụ ndụ T gbanwetụrụ n'ime ahụ onye ọrịa ka ịchọọ ma gbuo mkpụrụ ndụ kansa nke BCMA.

(11) Libmeldy

Ụlọ ọrụ: Orchard Therapeutics mepụtara.

Oge ịre ahịa: European Union kwadoro maka ndepụta na Disemba 2020.

Ngosipụta: Maka ọgwụgwọ metachromatic leukodystrophy (MLD).

Okwu: Libmeldy bụ usoro ọgwụgwọ mkpụrụ ndụ ihe nketa dabere na mgbanwe mkpụrụ ndụ lentiviral in vitro nke mkpụrụ ndụ CD34+ nke akpaaka.Data ụlọ ọgwụ na-egosi na otu infusion intravenous nke Libmeldy na-arụ ọrụ dị irè n'ịgbanwe usoro mmalite mmalite nke MLD yana nnukwu moto na nkwarụ uche na ndị ọrịa na-adịghị agwọ ọrịa nke otu afọ.

(12) Benoda

Ụlọ ọrụ: WuXi Junuo mebere ya.

Oge ịre ahịa: NMPA kwadoro na Septemba 2021.

Ngosipụta: Ọgwụgwọ nke nlọghachi azụ ma ọ bụ refractory nnukwu B-cell lymphoma (r / r LBCL) na ndị ọrịa toro eto mgbe usoro nke abụọ ma ọ bụ karịa usoro ọgwụgwọ.

Okwu: Benoda bụ ọgwụ mgbochi CD19 CAR-T gene therapy, na ọ bụkwa isi ngwaahịa nke WuXi Junuo.Ọ bụ ngwaahịa CAR-T nke abụọ akwadoro na China, belụsọ maka nnukwu lymphoma B-cell na-alaghachi azụ.Tụkwasị na nke ahụ, WuXi Junuo na-ezube ịmepụta ịgba ọgwụ Ruiki Orenza maka ọgwụgwọ nke mgbaàmà ndị ọzọ dị iche iche, gụnyere follicular lymphoma (FL), lymphoma mantle cell lymphoma (MCL), lymphocytic leukemia na-adịghị ala ala (CLL), nke abụọ na-agbasa nnukwu lymphoma B-cell (DLBCL) na nnukwu lymphoblastic leukemia (ALL).

(13) CARVYKTI

Ụlọ ọrụ: Ngwaahịa mbụ kwadoro Legend Bio.

Oge ịre ahịa: FDA kwadoro na February 2022.

Ngosipụta: Ọgwụgwọ nke nlọghachi azụ ma ọ bụ refractory multiple myeloma (R/R MM).

Nkwupụta: CARVYKTI (ciltacabtagene autoleucel, nke a na-akpọ Cilta-cel) bụ ọgwụgwọ mkpụrụ ndụ mgbochi nke CAR-T nwere ọgwụ mgbochi abụọ nwere otu ngalaba na-elekwasị anya na antigen B cell maturation (BCMA).Ihe omuma a gosiputara na CARVYKTI gosiputara onu ogugu nzaghachi nke ihe ruru 98% n'ime ndi oria nwere otutu myeloma na-achighari ma obu refractory nke natara usoro ọgwụgwọ anọ ma ọ bụ karịa tupu oge eruo, gụnyere proteasome inhibitors, immunomodulators, na mgbochi CD38 monoclonal antibodies.

2. In vivo gene therapy dabere na viral vectors

(1) Igbo/mụ nwoke ọzọ

Ụlọ ọrụ: Shenzhen Saibainuo Company mepụtara.

Oge ịre ahịa: akwadoro maka ndepụta na China na 2003.

Ngosipụta: Maka ọgwụgwọ squamous cell carcinoma nke isi na olu.

Okwu: Recombinant human p53 adenovirus injection Gendicine/Jinshengsheng bụ ọgwụ adenovirus vector gene therapy nwere ikike ọgụgụ isi nwere onwe ya nke Shenzhen Saibainuo Company nwere.Ọgwụ bụ nke nkịtị mmadụ tumor suppressor gene p53 na artificially modified recombinant replication-deficient Human adenovirus ụdị 5 bụ nke mmadụ adenovirus ụdị 5. Nke mbụ bụ isi usoro nke ọgwụ na-egosipụta mgbochi tumor mmetụta, na nke ikpeazụ bụ tumadi eme dị ka onye na-ebu.Vector nke adenovirus na-ebuga usoro ọgwụgwọ p53 n'ime cell ezubere iche, ma gosipụta etuto suppressor gene p53 na cell ezubere iche.Ngwaahịa ahụ nwere ike ịkwalite mkpụrụ ndụ ihe nketa mgbochi ọrịa cancer dị iche iche ma na-achịkwa ọrụ nke oncogenes dị iche iche, si otú a na-eme ka mmetụta mgbochi tumor nke ahụ dịkwuo elu ma nweta nzube nke igbu etuto ahụ.

(2) Rigvir

Ụlọ ọrụ: Ụlọ ọrụ Latvia bụ Latima mepụtara.

Oge ịre ahịa: Ekwenyere na Latvia na 2004.

Ngosipụta: Maka ọgwụgwọ nke melanoma.

Okwu: Rigvir bụ usoro ọgwụgwọ mkpụrụ ndụ ihe nketa dabere na mkpụrụ ndụ ihe nketa ECHO-7 enterovirus vector, nke ejirila na Latvia, Estonia, Poland, Armenia, Belarus na ebe ndị ọzọ, a na-edekwa ya na EMA nke European Union..Usoro ụlọ ọgwụ n'ime afọ iri gara aga egosila na nje Rigvir oncolytic dị mma ma dị irè, ma nwee ike melite ọnụego ndụ nke ndị ọrịa melanoma ugboro 4-6.Tụkwasị na nke ahụ, ọgwụgwọ ahụ dịkwa mma maka ọrịa cancer ndị ọzọ dị iche iche, gụnyere ọrịa cancer colorectal, cancer pancreatic, cancer eriri afo.ọrịa kansa, kansa akụrụ, ọrịa prostate, kansa akpa ume, kansa uterine, lymphosarcoma, wdg.

(3) Oncorine/Ankerui

Ụlọ ọrụ: Emepụtara ya Shanghai Sunway Biotechnology Co., Ltd.

Oge ịre ahịa: akwadoro maka ndepụta na China na 2005.

Ngosipụta: Ọgwụgwọ etuto isi na olu, ọrịa kansa imeju, kansa pancreatic, kansa cervical na ọrịa kansa ndị ọzọ.

Nkwupụta: Oncorine bụ ngwaahịa ọgwụgwọ mkpụrụ ndụ oncolytic na-eji adenovirus dị ka vector.The enwetara oncolytic adenovirus nwere ike imepụtaghachi kpọmkwem na etuto ahụ na-adịghị ma ọ bụ ihe na-adịghị mma p53 gene, na-akpata tumor cell lysis, si otú na-egbu tumor cell.na-emebighị sel nkịtị.Nsonaazụ ụlọ ọgwụ na-egosi na Anke Rui nwere ezigbo nchekwa na ịdị irè maka ụdị etuto ahụ dị njọ.

(4) Glybera

Ụlọ ọrụ: UniQre mebere ya.

Oge ịre ahịa: akwadoro na Europe na 2012.

Ngosipụta: Ọgwụgwọ ụkọ lipoprotein lipase (LPLD) nwere nnukwu ọrịa pancreatitis ma ọ bụ ugboro ugboro n'agbanyeghị nri abụba amachibidoro.

Okwu: Glybera (alipogene tiparvovec) bụ ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nketa dabere na AAV dị ka vector.Usoro ọgwụgwọ a na-eji AAV dị ka vector na-ebufe mkpụrụ ndụ ọgwụgwọ LPL n'ime sel anụ ahụ, nke mere na mkpụrụ ndụ kwekọrọ na ya nwere ike ịmepụta ụfọdụ lipoprotein lipase, Ọ na-ekere òkè na-ebelata ọrịa, na ọgwụgwọ a dị irè ruo ogologo oge mgbe otu nchịkwa gasịrị (mmetụta ahụ nwere ike ịdịru ruo ọtụtụ afọ).E wepụrụ ọgwụ ahụ na 2017, na ihe kpatara iwepụ ya nwere ike jikọta ya na ihe abụọ: ọnụ ahịa dị oke elu na oke ahịa ahịa.Ọnụ ego nke otu ọgwụgwọ ọgwụ ahụ ruru ihe ruru nde dollar US 1, ma ọ bụ naanị otu onye ọrịa zụrụ ma jiri ya mee ihe.Ọ bụ ezie na ụlọ ọrụ ịnshọransị ahụike kwụghachiri ya dollar 900,000, ọ bụkwa ibu arọ maka ụlọ ọrụ ịnshọransị ahụ.Tụkwasị na nke ahụ, ihe ngosi maka ọgwụ ahụ dị oke ụkọ, na ọnụ ọgụgụ nke ihe dị ka 1 n'ime 1 nde na ọnụ ọgụgụ dị elu nke nchọpụta na-ezighị ezi.

(5) Ikwu okwu

Ụlọ ọrụ: Amgen mepụtara.

Oge ịre ahịa: Na 2015, akwadoro ya maka ịdebanye aha na United States na European Union.

Ngosipụta: Ọgwụgwọ nke ọnya melanoma nke enweghị ike iwepụ kpamkpam site na ịwa ahụ.

Okwu: Imlygic bụ genetically gbanwetụrụ (ihichapụ ya ICP34.5 na ICP47 gene iberibe, na ịtinye mmadụ granulocyte-macrophage colony-stimulating factor GM-CSF gene n'ime nje) attenuated herpes simplex virus ụdị 1 (HSV-1) oncolytic nje, nke mbụ FDA-approved nje virus.Usoro nchịkwa bụ injection intralesional.Ịgbanye ozugbo n'ime ọnya melanoma nwere ike ime ka mgbawa nke mkpụrụ ndụ tumo ma hapụ antigens sitere na tumor na GM-CSF iji kwalite nzaghachi mgbochi tumor.

(6) Luxturna

Ụlọ ọrụ: Spark Therapeutics, onye enyemaka Roche mepụtara.

Oge ịzụ ahịa: FDA kwadoro na 2017, wee kwado ya maka ịzụ ahịa na Europe na 2018.

Ngosipụta: Maka ọgwụgwọ ụmụaka na ndị okenye nwere ọhụụ ọhụụ n'ihi mmụgharị dị na mkpụrụ ndụ okpukpu abụọ nke RPE65 ma nwee ọnụọgụ zuru oke nke mkpụrụ ndụ retinal nwere ike ime.

Okwu: Luxturna bụ usoro ọgwụgwọ mkpụrụ ndụ sitere na AAV nke a na-enye site na ntụtụ subretinal.Usoro ọgwụgwọ mkpụrụ ndụ ihe nketa na-eji AAV2 dị ka onye na-ebu ibu iji webata ọrụ nke mkpụrụ ndụ RPE65 nkịtị n'ime sel retinal nke onye ọrịa, nke mere na mkpụrụ ndụ kwekọrọ na-egosipụta protein RPE65 nkịtị iji kwụọ ụgwọ maka ntụpọ nke protein RPE65 nke onye ọrịa, si otú ahụ meziwanye ọhụụ onye ọrịa.

(7) Zolgensma

Ụlọ ọrụ: AveXis mepụtara, enyemaka nke Novartis.

Oge ịre ahịa: FDA kwadoro na Mee 2019.

Ngosipụta: Ọgwụgwọ nke atrophy muscular spinal (Spinal Muscular Atrophy, SMA) ndị ọrịa nọ n'okpuru afọ 2.

Nkọwa: Zolgensma bụ ọgwụgwọ mkpụrụ ndụ ihe nketa dabere na vector AAV.Ọgwụ a bụ naanị atụmatụ ọgwụgwọ otu oge maka atrophy muscular spinal nke akwadoro maka ire ahịa n'ụwa.ibe, bụ ọganihu dị ịrịba ama.Usoro ọgwụgwọ mkpụrụ ndụ ihe nketa a na-eji vector scAAV9 ewebata mkpụrụ ndụ SMN1 nkịtị n'ime ndị ọrịa site na infusion intravenous, na-emepụta protein SMN1 nkịtị, si otú a na-emeziwanye ọrụ nke mkpụrụ ndụ emetụtara dị ka neurons moto.N'ụzọ dị iche, ọgwụ SMA Spinraza na Evrysdi chọrọ ka a na-eme ya ugboro ugboro ruo ogologo oge, na Spinraza a na-enye ya dị ka ogwu ogwu n'ime ọnwa anọ ọ bụla, yana Evrysdi, ọgwụ ọnụ kwa ụbọchị.

(8) Na-akpachapụ anya

Ụlọ ọrụ: Mepụtara ya Daiichi Sankyo Company Limited (TYO: 4568).

Oge ịre ahịa: Nkwenye ọnọdụ sitere na Ministri Ahụike, Ọrụ na ọdịmma Japan (MHLW) na June 2021.

Ngosipụta: Maka ọgwụgwọ glioma dị njọ.

Nkwupụta: Delytact bụ ngwaahịa ọgwụgwọ mkpụrụ ndụ oncolytic nke anọ akwadoro n'ụwa niile yana ngwaahịa nje oncolytic izizi akwadoro maka ọgwụgwọ glioma na-adịghị mma.Delytact bụ nje virus oncolytic nke herpes simplex ụdị 1 (HSV-1) nke Dr. Todo na ndị ọrụ ibe mepụtara.Delytact na-ewebata mmụgharị nhichapụ ọzọ n'ime G207 genome nke ọgbọ nke abụọ HSV-1, na-eme ka mmeghari nhọrọ ya na mkpụrụ ndụ kansa na ntinye nke nzaghachi mgbochi tumor, ebe ọ na-ejigide profaịlụ nchekwa dị elu.Delytact bụ ọgbọ nke atọ oncolytic HSV-1 ugbu a na nyocha ụlọ ọgwụ.Nkwenye nke Delytact na Japan gbadoro ụkwụ na nnwale ụlọ ọgwụ nwere otu akụkụ nke abụọ.N'ime ndị ọrịa nwere glioblastoma ugboro ugboro, Delytact zutere isi njedebe nke ndụ otu afọ, nsonaazụ ya gosipụtara na Delytact rụrụ nke ọma karịa G207.Mmụgharị siri ike na ọrụ antitumor dị elu.Nke a dị irè na ụdị tumor siri ike gụnyere ara, prostate, schwannoma, nasopharyngeal, hepatocellular, colorectal, malignant peripheral nerve sheath tumors na thyroid cancer.

(9) Ugboro

Ụlọ ọrụ: Mepụtara PTC Therapeutics, Inc. (NASDAQ: PTCT).

Oge ịre ahịa: EU kwadoro na Julaị 2022.

Ngosipụta: Maka ụkọ L-amino acid decarboxylase (AADC), nke akwadoro maka ọgwụgwọ ndị ọrịa dị ọnwa 18 na karịa.

Okwu: Upstaza™ (eladocagene exuparvovec) bụ ọgwụgwọ mkpụrụ ndụ in vivo na-eji ụdị nje 2 (AAV2) metụtara adeno dị ka vector.Onye ọrịa ahụ na-arịa ọrịa n'ihi mmụgharị na mkpụrụ ndụ ihe nketa na-etinye enzyme AADC.AAV2 na-ebu mkpụrụ ndụ dị mma na-edobe enzyme AADC.A na-enweta mmetụta ọgwụgwọ ahụ n'ụdị nkwụghachi ụgwọ mkpụrụ ndụ ihe nketa.Na tiori, otu dose dị irè ruo ogologo oge.Ọ bụ ọgwụgwọ mkpụrụ ndụ ihe nketa nke mbụ a gbabara ozugbo n'ime ụbụrụ.Ikike ịre ahịa na-emetụta mba 27 niile EU, yana Iceland, Norway na Liechtenstein.

(9) Roctavian

Ụlọ ọrụ: BioMarin Pharmaceutical (BioMarin) mepụtara.

Oge ịre ahịa: EU kwadoro na August 2022.

Ngosipụta: Maka ọgwụgwọ nke ndị ọrịa toro eto nwere nnukwu hemophilia A na-enweghị akụkọ ihe mere eme nke mgbochi FVIII na mgbochi AAV5 adịghị mma.

Okwu: Roctavian (valoctocogene roxaparvovec) na-eji AAV5 dị ka vector ma na-eji HLP na-akwalite imeju mmadụ na-eme ka ngosipụta nke coagulation mmadụ asatọ (FVIII) na ngalaba B ehichapụ.Mkpebi nke European Commission kwadoro ịre ahịa nke valoctocogene roxaparvovec dabere na mkpokọta data nke mmemme mmepe ụlọ ọgwụ ọgwụ.N'ime ha, usoro nke atọ nke ụlọ ọgwụ GENEr8-1 gosiri na e jiri ya tụnyere data nke afọ tupu edebanye aha, mgbe otu infusion nke valoctocogene roxaparvovec gasịrị, ndị isiokwu nwere ọnụ ọgụgụ ọbara ọgbụgba na-ebelata kwa afọ (ABR), obere ojiji nke recombinant factor VIII (F8) protein nkwadebe, ma ọ bụ mmụba dị ukwuu na ọrụ F8 n'ime ọbara ahụ.Mgbe izu anọ nke ọgwụgwọ gasịrị, iji F8 ndị mmadụ na-eme kwa afọ yana ABR chọrọ ọgwụgwọ belatara site na 99% na 84%, n'otu n'otu, ọdịiche dị ịrịba ama (p<0.001).Profaịlụ nchekwa ahụ dị mma, na-enweghị ihe ọ bụla na-enwe ihe mgbochi F8, ihe ọjọọ, ma ọ bụ mmetụta thrombotic, na enweghị ihe omume ọjọọ metụtara ọgwụgwọ (SAEs).

3. Obere ọgwụ nucleic acid

(1) Vitravene

Ụlọ ọrụ: Ejikọtara ọnụ nke Ionis Pharma (nke bụbu Isis Pharma) na Novartis.

Oge ịre ahịa: FDA na EU EMA kwadoro na 1998 na 1999.

Ngosipụta: Maka ọgwụgwọ cytomegalovirus retinitis na ndị ọrịa nwere nje HIV.

Nkwuputa: Vitravene bụ ọgwụ oligonucleotide antisense na ọgwụ oligonucleotide mbụ kwadoro maka ịzụ ahịa n'ụwa.Ná mmalite nke ahịa, ahịa ahịa maka ọgwụ mgbochi cytomegalovirus dị ngwa ngwa;mgbe ahụ n'ihi mmepe nke ọgwụgwọ antiretroviral na-arụsi ọrụ ike, ọnụ ọgụgụ nke cytomegalovirus gbadara nke ọma.N'ihi ọnụ ahịa ahịa dị ala, ewepụtara ọgwụ ahụ na 2002 na 2006 ndọrọ ego na mba EU na US.

(2) Macugen

Ụlọ ọrụ: Pfizer na Eyetech mebere ya.

Oge ịre ahịa: Ekwenyere maka ịdebanye aha na United States na 2004.

Ngosipụta: Maka ọgwụgwọ nke ọrịa macular degeneration metụtara afọ neovascular.

Nkwupụta: Macugen bụ ọgwụ oligonucleotide nke pegylated emezigharịrị nke nwere ike ịche ma jikọta ya na vaskụla endothelial growth factor (VEGF165 isoform), a na-enye ya site na intravitreal injection.

(3) Defitelio

Ụlọ ọrụ: Jazz mepụtara.

Oge ịre ahịa: Ndị European Union kwadoro na 2013, FDA kwadoro na March 2016.

Ngosipụta: Maka ọgwụgwọ ọrịa hepatic venule occlusive nke jikọtara ya na arụ ọrụ gbasara akụrụ ma ọ bụ pulmonary mgbe transplantation hematopoietic stem cell.

Okwu: Defitelio bụ ọgwụ oligonucleotide, ngwakọta nke oligonucleotides nwere ihe plasmin.Ewepụrụ ya na 2009 maka ebumnuche azụmahịa.

(4) Kynamro

Ụlọ ọrụ: Ionis Pharma na Kastle mebere ya.

Oge ịre ahịa: Ekwenyere na United States dị ka ọgwụ ụmụ mgbei na 2013.

Ngosipụta: Maka ọgwụgwọ adjuvant nke homozygous familial hypercholesterolemia.

Nkwuputa: Kynamro bụ ọgwụ oligonucleotide antisense, antisense oligonucleotide na-ezubere apo B-100 mRNA mmadụ.A na-enye Kynamro dị ka 200 mg subcutaneously otu ugboro n'izu.

(5) Spinraza

Ụlọ ọrụ: Ionis Pharmaceuticals mepụtara.

Oge ịre ahịa: FDA kwadoro na Disemba 2016.

Ngosipụta: Maka ọgwụgwọ nke spinal muscular atrophy (SMA).

Okwu: Spinraza (nusinersen) bụ ọgwụ antisense oligonucleotide.Spinraza nwere ike ịgbanwe splicing RNA nke mkpụrụ ndụ SMN2 site na ijikọ na saịtị splicing nke SMN2 exon 7, si otú ahụ na-abawanye mmepụta nke protein SMN na-arụ ọrụ nke ọma.N'August 2016, BIOGEN Corporation gosipụtara nhọrọ ya iji nweta ikike zuru ụwa ọnụ nke Spinraza.Spinraza malitere nnwale ụlọ ọgwụ mbụ ya na ụmụ mmadụ na 2011. N'ime naanị afọ 5, FDA kwadoro ya na 2016, na-egosipụta nkwenye zuru oke nke FDA maka ịdị irè ya.A kwadoro ọgwụ ahụ maka ịzụ ahịa na China na Eprel 2019. Usoro nkwenye zuru oke nke Spinraza na China bụ ihe na-erughị ọnwa 6.Ọ bụ afọ 2 na ọnwa 2 kemgbe akwadoro Spinraza na United States.Dị otú ahụ a blockbuster mba ọzọ obere ọrịa ọhụrụ ọgwụ dị na Ọsọ nke ndepụta na China adịlarị ngwa ngwa.Nke a bụkwa n'ihi "Nrịbama na mwepụta nke ndepụta mbụ nke ọgwụ ọhụrụ nke mba ofesi achọrọ ngwa ngwa maka nyocha ụlọ ọgwụ" nke Center for Drug Evaluation nyere na November 1, 2018, nke etinyere na nke mbụ nke 40 isi ọgwụ ọhụrụ mba ọzọ maka nyocha ngwa ngwa, na Spinraza họọrọ.

(6) Ọpụpụ 51

Ụlọ ọrụ: AVI BioPharma mepụtara (nke emechara aha ya bụ Sarepta Therapeutics).

Oge ịre ahịa: FDA kwadoro na Septemba 2016.

Ngosipụta: Maka ọgwụgwọ Duchenne muscular dystrophy (DMD) na mkpụrụ ndụ ihe nketa DMD na exon 51 skipping gene.

Okwu: Exondys 51 bụ ọgwụ antisense oligonucleotide.Oligonucleotide antisense nwere ike jikọta na exon 51 ọnọdụ nke pre-mRNA nke mkpụrụ ndụ DMD, na-ebute nguzobe nke mRNA tozuru okè.Mpụpụ, si otú a na-edozi akụkụ nke mRNA ọgụgụ isi, na-enyere onye ọrịa aka ịmepụta ụdị dystrophin ụfọdụ na-arụ ọrụ nke dị mkpụmkpụ karịa protein nkịtị, si otú ahụ na-eme ka mgbaàmà onye ọrịa dịkwuo mma.

(7) Tegsedi

Ụlọ ọrụ: Ionis Pharmaceuticals mepụtara.

Oge ịre ahịa: European Union kwadoro maka ịre ahịa na Julaị 2018.

Ngosipụta: Maka ọgwụgwọ transthyretin amyloidosis (hATTR) nke ketara eketa.

Nkwupụta: Tegsedi bụ ọgwụ antisense oligonucleotide na-ezubere transthyretin mRNA.Ọ bụ ọgwụ izizi akwadoro n'ụwa maka ọgwụgwọ haTTR.Usoro nchịkwa bụ ntụtụ subcutaneous.Ọgwụ ahụ na-ebelata mmepụta nke protein ATTR site n'ịtụkwasị mRNA nke transthyretin (ATTR), ma nwee oke uru bara uru na ọgwụgwọ ATTR.Ọkwa ọrịa ma ọ bụ ọnụnọ cardiomyopathy adịghị mkpa.

(8) Onpattro

Ụlọ ọrụ: Alnylam na Sanofi mebere ya.

Oge ịre ahịa: Ekwenyere maka ndepụta na United States na 2018.

Ngosipụta: Maka ọgwụgwọ transthyretin amyloidosis (hATTR) nke ketara eketa.

Okwu: Onpattro bụ ọgwụ siRNA na-ezubere transthyretin mRNA, nke na-ebelata mmepụta nke protein ATTR n'ime imeju na nchikota nke amyloid nkwụnye ego n'ime irighiri akwara site na ichu mRNA nke transthyretin (ATTR)., si otú ahụ na-emeziwanye ma na-ebelata mgbaàmà ọrịa.

(9) Givlaari

Ụlọ ọrụ: Alnylam Corporation mepụtara.

Oge ịre ahịa: FDA kwadoro na Nọvemba 2019.

Ngosipụta: Maka ọgwụgwọ nnukwu hepatic porphyria (AHP) na ndị okenye.

Nkwupụta: Givlaari bụ ọgwụ siRNA, ọgwụ siRNA nke abụọ akwadoro maka ire ahịa mgbe Onpattro gachara.A na-enye ọgwụ ahụ na subcutaneously ma lekwasịrị anya mRNA maka mmebi nke protein ALAS1.Ọgwụgwọ Givlaari kwa ọnwa nwere ike belata ọkwa ALAS1 n'ime imeju nke ukwuu, wee si otú a belata ọkwa neurotoxic ALA na PBG n'ụdị kwesịrị ekwesị, wee si otú a belata mgbaàmà ọrịa onye ọrịa.Ihe omuma a gosiputara na ndi oria Givlaari gwọtara nwere mbelata 74% n'onu ogugu oria oria ma e jiri ya tụnyere otu placebo.

(10) Vyondys53

Ụlọ ọrụ: Sarepta Therapeutics mepụtara.

Oge ịre ahịa: FDA kwadoro na Disemba 2019.

Ngosipụta: Maka ọgwụgwọ nke ndị ọrịa DMD nwere dystrophin gene exon 53 splice mutation.

Okwu: Vyondys 53 bụ ọgwụ oligonucleotide antisense.Ọgwụ oligonucleotide na-elekwasị anya n'usoro nhazi nke dystrophin mRNA precursor.Na usoro na-apụtaghị ìhè nke dystrophin mRNA precursor, Exon 53 dị na mpụga ekewapụrụ akụkụ ya, ya bụ na ọ nọghị na mRNA tozuru etozu, wee mee ya ka ọ mepụta protein dystrophin gbajiri agbaji mana ọ ka na-arụ ọrụ, wee si otú a na-emewanye ikike mmega ahụ na ndị ọrịa.

(11) Waylivra

Ụlọ ọrụ: Mepụtara site na Ionis Pharmaceuticals na enyemaka ya Akcea Therapeutics.

Oge ịre ahịa: Ndị European Medicines Agency (EMA) kwadoro na Mee 2019.

Ngosipụta: Dị ka ọgwụgwọ mgbakwunye na nri a na-achịkwa na ndị okenye nwere ọrịa chylomicronemia familial (FCS).

Nkwupụta: Waylivra bụ ọgwụ oligonucleotide antisense, nke bụ ọgwụ izizi akwadoro maka ọgwụgwọ FCS n'ụwa.

(12) Leqvio

Ụlọ ọrụ: Novartis mepụtara.

Oge ịre ahịa: EU kwadoro na Disemba 2020.

Ngosipụta: Maka ọgwụgwọ nke okenye hypercholesterolemia (heterozygous familial and non-familial) ma ọ bụ agwakọta dyslipidemia.

Okwu: Leqvio bụ ọgwụ siRNA na-ezubere PCSK9 mRNA.Ọ bụ usoro ọgwụgwọ siRNA nke na-ebelata cholesterol (LDL-C) nke mbụ n'ụwa.Usoro nchịkwa bụ ntụtụ subcutaneous.Ọgwụ na-arụ ọrụ site na ndabichi RNA iji wedata ọkwa protein PCSK9, nke n'aka nke ya na-ebelata ọkwa LDL-C.Data ụlọ ọgwụ na-egosi na Leqvio nwere ike ibelata LDL-C site na ihe dịka 50% n'ime ndị ọrịa enweghị ike ibelata ọkwa LDL-C na ọkwa ebumnuche n'agbanyeghị oke statins anabatara.

(13) Oxlumo

Ụlọ ọrụ: Alnylam Pharmaceuticals mepụtara.

Oge ịre ahịa: EU kwadoro na Nọvemba 2020.

Ngosipụta: Maka ọgwụgwọ nke isi hyperoxaluria ụdị 1 (PH1).

Nkwupụta: Oxlumo bụ ọgwụ siRNA na-ezubere hydroxy acid oxidase 1 (HAO1) ​​mRNA, nke a na-enye ya n'okpuru akpụkpọ ahụ.Emepụtara ọgwụ ahụ site na iji teknụzụ njikọ njikọta nke ESC-GalNAc nke Alnylam kachasị ọhụrụ, nke na-enyere siRNA ndị a na-enye n'okpuru akpụkpọ ahụ aka inwe ntachi obi na arụmọrụ dị ukwuu.Ọgwụ ahụ na-elekwasị anya nbibi ma ọ bụ mgbochi nke hydroxy acid oxidase 1 (HAO1) ​​mRNA, na-ebelata ọkwa nke glycolate oxidase n'ime imeju, wee na-eri mkpụrụ nke achọrọ maka mmepụta nke oxalate ma belata mmepụta nke oxalate iji chịkwaa ọganihu ọrịa ma melite mgbaàmà ọrịa na ndị ọrịa.

(14) Viltepso

Ụlọ ọrụ: NS Pharma mebere ya, onye enyemaka nke Nippon Shinyaku.

Oge ịre ahịa: FDA kwadoro na Ọgọst 2020.

Ngosipụta: Maka ọgwụgwọ Duchenne muscular dystrophy (DMD) na mkpụrụ ndụ ihe nketa DMD na exon 53 skipping gene.

Okwu: Viltepso bụ ọgwụ phosphorodiamide morpholino oligonucleotide.Ọgwụ oligonucleotide a nwere ike jikọta na exon 53 ọnọdụ nke pre-mRNA nke mkpụrụ ndụ DMD, na-ebute nguzobe nke mRNA tozuru okè.A na-ewepụ exon ahụ n'otu akụkụ, si otú ahụ na-edozi akụkụ nke mRNA ọgụgụ isi, na-enyere onye ọrịa aka ịmepụta ụfọdụ ụdị dystrophin na-arụ ọrụ nke dị mkpụmkpụ karịa protein nkịtị, si otú ahụ na-eme ka mgbaàmà onye ọrịa dịkwuo mma.

(15) Amvuttra (vutrisiran)

Ụlọ ọrụ: Alnylam Pharmaceuticals mepụtara.

Oge ịre ahịa: FDA kwadoro na June 2022.

Ngosipụta: Maka ọgwụgwọ nke ndị okenye ketara eketa transthyretin amyloidosis na polyneuropathy (hATTR-PN).

Nkwupụta: Amvuttra (Vutrisiran) bụ ọgwụ siRNA na-ezubere transthyretin (ATTR) mRNA, nke a na-enye site na ntụtụ subcutaneous.Emebere Vutrisiran dabere na Alnylam's Enhanced Stabilization Chemistry (ESC) -GalNAc conjugated nnyefe n'elu ikpo okwu na ụba ike na metabolic kwụsie ike.Nkwenye nke ọgwụgwọ ahụ dabere na data 9-ọnwa sitere na usoro ọmụmụ ụlọ ọgwụ nke III (HELIOS-A), na-egosi na ọgwụgwọ ahụ kwalitere ihe mgbaàmà nke hATTR-PN, na ihe karịrị 50% nke ndị ọrịa na-atụgharị ma ọ bụ kwụsị ọganihu.

4. Ọgwụ ọgwụgwọ mkpụrụ ndụ ndị ọzọ

(1) Rexin-G

Ụlọ ọrụ: Epeius Biotech mepụtara.

Oge ịre ahịa: Ndị nchịkwa nri na ọgwụ na Philippines (BFAD) kwadoro na 2005.

Ngosipụta: Maka ọgwụgwọ ọrịa kansa dị elu nke na-eguzogide ọgwụ chemotherapy.

Okwu: Rexin-G bụ ogwugwu nanoparticle nke ejiri mkpụrụ ndụ ihe nketa.Ọ na-ewebata cyclin G1 mutant gene n'ime mkpụrụ ndụ ebumnuche site na vector retroviral iji gbuo etuto siri ike kpọmkwem.Usoro nchịkwa bụ infusion intravenous.Dị ka ọgwụ a na-ezubere maka tumor nke na-achọsi ike ma na-ebibi mkpụrụ ndụ cancer metastatic, ọ nwere mmetụta ụfọdụ na ndị ọrịa na-adịghị arụ ọrụ megide ọgwụ ndị ọzọ nke ọrịa cancer, gụnyere ndị ezubere iche maka ihe ndị dị ndụ.

(2) Neovasculgen

Ụlọ ọrụ: Ụlọ ọrụ cell stem cell mepụtara.

Oge ndepụta: Ekwenyere maka ịdebanye aha na Russia na Disemba 7, 2011, wee depụta ya na Ukraine na 2013.

Ngosipụta: Maka ọgwụgwọ ọrịa akwara dị n'akụkụ, gụnyere ischemia siri ike.

Nkọwa: Neovasculgen bụ usoro ọgwụgwọ DNA plasmid nke dabeere na mkpụrụ ndụ ihe nketa nke vaskụla endothelial growth factor (VEGF) 165 na-arụ na ọkpụkpụ plasmid ma tinye ya n'ime ndị ọrịa.

(3) Collategene

Ụlọ ọrụ: Ụlọ akwụkwọ mahadum Osaka na ụlọ ọrụ na-emepe emepe.

Oge ndepụta: Ministri ahụike, ọrụ na ọdịmma nke Japan kwadoro maka ịdepụta na August 2019.

Ngosipụta: Ọgwụgwọ nke ischemia dị oke ala dị ala.

Okwu: Collategene bụ ọgwụgwọ mkpụrụ ndụ ihe nketa nke plasmid, ọgwụ ọgwụgwọ mkpụrụ ndụ ihe nketa Japan izizi nke AnGes mepụtara.Akụkụ bụ isi nke ọgwụ a bụ plasmid gba ọtọ nke nwere usoro mkpụrụ ndụ hepatocyte na-eto eto (HGF).Ọ bụrụ na a na-agbanye ọgwụ ahụ n'ime akwara nke akụkụ ahụ dị ala, HGF a gosipụtara ga-akwalite nhazi nke arịa ọbara ọhụrụ gburugburu arịa ọbara.Nnwale ụlọ ọgwụ ekwenyela na ọ dị irè n'ịkwalite ọnya.

N'ikpeazụ