Mohloli: WuXi AppTec

Lilemong tsa morao tjena, lefapha la phekolo ea RNA le bontšitse mokhoa o phatlohileng-lilemong tse 5 tse fetileng feela, FDA e amohetse liphekolo tsa RNA tse 11, ’me palo ena e bile e feta kakaretso ea liphekolo tsa RNA tse neng li amohetsoe pele!Ha ho bapisoa le liphekolo tsa setso, phekolo ea RNA e ka hlahisa mekhoa ea phekolo e lebisitsoeng ka potlako ka sekhahla se phahameng sa katleho hafeela tatellano ea lefutso ea sepheo se tsejoa.Ka lehlakoreng le leng, liphekolo tse ngata tsa RNA li ntse li fumaneha feela bakeng sa ho phekola mafu a sa tloaelehang, 'me nts'etsopele ea liphekolo tse joalo e ntse e tobana le mathata a mangata mabapi le ho tšoarella ha phekolo, polokeho le pelehi.Sehloohong sa kajeno, thesehlopha sa dikahare sa WuXi AppTec se tla lekola kgatelopele lefapheng la kalafo ya RNA selemong se fetileng, mme re lebelle bokamoso ba sebaka sena se hlahang le babali.

▲ Liphekolo kapa liente tsa RNA tse 11 li amohetsoe ke FDA lilemong tse 5 tse fetileng.

Ho tloha ho mafu a sa tloaelehang ho ea ho mafu a tloaelehileng, lipalesa tse ngata li thunya

Seoa se secha sa moqhaka, ente ea mRNA e hlahile ka ntle ho sebaka mme e fumane tlhokomelo e pharalletseng ho tsoa indastering.Ka mor'a mookatleho ea nts'etsopele ea liente tsa mafu a tšoaetsanoang, phephetso e 'ngoe e kholo e tobaneng le theknoloji ea mRNA ke ho atolosa sebaka sa ts'ebeliso ea kalafo le thibelo ea mafu a mangata.
Har'a bona,liente tsa mofetše ka bomong ke karolo ea bohlokoa ea ts'ebeliso ea theknoloji ea mRNA, hape re bone liphetho tse ntle tsa bongaka tsa liente tse ngata tsa mofetše selemong sena.Khoeling ena feela, ente e ikemetseng ea mofets'e e kopantsoeng ke Moderna le Merck, e kopantsoe le PD-1 inhibitor Keytruda,fokotsa kotsiea ho pheta-pheta kapa lefu ho bakuli ba nang le melanoma ea sethaleng sa III le IV ka mor'a ho tsosolosoa ka ho feletseng ha hlahala ka 44% (ho bapisoa le Keytruda monotherapy).Phatlalatso ea boralitaba e bontšitse hore lena ke lekhetlo la pele ha ente ea mofetše oa mRNA e bonts'a katleho kalafong ea melanoma tekong ea bongaka e sa reroang, e leng ketsahalo ea bohlokoa ntlafatsong ea liente tsa mofetše oa mRNA.
Ntle le moo, liente tsa mRNA le tsona li ka ntlafatsa phello ea kalafo ea kalafo ea lisele.Ka mohlala, phuputso e entsoeng ke BioNTech e bontšitse hore haeba bakuli ba qala ho kenngoa ka tekanyo e tlaase ea phekolo ea CAR-T e lebisitsoeng ho CLDN6.BNT211, ebe e kenngoa ka ente ea mRNA e kenyang CLDN6, e ka susumetsa lisele tsa CAR-T ka ho hlahisa CLDN6 holim'a lisele tse hlahisang antigen.Amplification, ka hona, e ntlafatsa phello ea anticancer.Liphetho tsa pele li bonts'itse hore bakuli ba 4 ho ba 5 ba fumaneng kalafo e kopaneng ba fihletse karabelo e sa fellang, kapa 80%.

Ntle le kalafo ea mRNA, kalafo ea oligonucleotide le kalafo ea RNAi le tsona li fumane litholoana tse ntle ho holiseng bongata ba mafu.Kalafo e sa foleng ea lefu la sebete la mofuta oa B, hoo e ka bang karolo ea 30 lekholong ea bakuli ha e khone ho lemoha antigen ea hepatitis B le kokoana-hloko ea hepatitis B ka mor'a ho sebelisa oligonucleotide therapy.bepirovirsen e kopantsoe hammoho ke GSK le Ionisbakeng sa libeke tse 24.Ho bakuli ba bang, esita le libeke tse 24 ka mor'a ho emisa kalafo, matšoao ana a lefu la sebete la mofuta oa B a ne a ntse a sa bonahale 'meleng.
Ka tšohanyetso, phekolo ea RNAiVIR-2218 e ntlafalitsoeng ka kopanelo ke Vir Biotechnology le Alnylam e ile ea kopanngoaka interferon α, le litekong tsa kliniki tsa mohato oa 2, hoo e ka bang 30% ea bakuli ba sa foleng ba lefu la sebete la mofuta oa B le bona ba ile ba hlōleha ho lemoha hepatitis B surface antigen (HBsAg).Ho phaella moo, bakuli bana ba ile ba hlahisa li-antibodies khahlanong le protheine ea hepatitis B, e bontšang karabelo e ntle ea tsamaiso ea 'mele ea ho itšireletsa mafung.Ha e nka liphetho tsena hammoho, indasteri e supa hore kalafo ea RNA e ka ba senotlolo sa pheko e sebetsang ea lefu la sebete la mofuta oa B.
Sena e ka ba qalo feela ea phekolo ea RNA bakeng sa mafu a tloaelehileng.Ho latela phaephe ea Alnylam ea R&D, e boetse e nts'etsapele liphekolo tsa RNAi bakeng sa kalafo ea khatello ea mali, lefu la Alzheimer, le steatohepatitis e seng joala, 'me bokamoso bo bohlokoa ho lebella.

Ho kenella ka har'a botlolo ea phepelo ea kalafo ea RNA

Phano ea kalafo ea RNA ke e 'ngoe ea litšitiso tse fokotsang ts'ebeliso ea eona.Bo-ramahlale ba boetse ba nts'etsapele mahlale a fapaneng ho fana ka kalafo ea RNA ka kotloloho ho litho le lisele tse ling ntle le sebete.
E 'ngoe ea mekhoa e ka bang teng ke ho "tlama" li-RNA tsa kalafo ka limolek'hule tse ikhethileng ka lisele .Mohlala, Avidity Biosciences e sa tsoa phatlalatsa hore sethala sa eona sa theknoloji se ka kopanya li-antibodies tsa monoclonal ho oligonucleotides.ka katleho tlama siRNAs.e rometsoeng ho mesifa ea marapo.Phatlalatso ea khatiso e bontšitse hore lena ke lekhetlo la pele leo siRNA e ka lebisoang ka katleho le ho nehelanoa ka mesifa ea mesifa ea motho, e leng katleho e kholo tšimong ea phekolo ea RNA.

Mohloli oa setšoantšo: 123RF

Ntle le theknoloji ea conjugation ea antibody, lik'hamphani tse 'maloa tse hlahisang lipid nanoparticles (LNP) le tsona li "ntlafatsa" bajari ba joalo.Ka mohlala, ReCode Therapeutice sebelisa Selective Organ Targeting LNP Technology (SORT) ea eona e ikhethang ho fana ka mefuta e fapaneng ea phekolo ea RNA matšoafong, spleen, sebete le litho tse ling.Selemong sena, k'hamphani e phatlalalitse ho phethoa ha lichelete tsa lichelete tsa US $ 200 milione Series B, le mafapha a lichelete a Pfizer, Bayer, Amgen, Sanofi le lik'hamphani tse ling tse kholo tsa meriana tse kenyang letsoho matsete.Kernal Biologics, e ileng ea boela ea fumana liranta tse limilione tse 25 ka lichelete tsa Series A selemong sena, e boetse e hlahisa LNP e sa bokelleng sebeteng, empa e ka fana ka mRNA ho lebisa lisele tse kang boko kapa lihlahala tse itseng.
Orbital Therapeutics, e qalileng selemong sena, e boetse e nka phepelo ea phekolo ea RNA e le tataiso ea bohlokoa ea nts'etsopele.Ka ho kopanya theknoloji ea RNA le mekhoa ea ho fana ka thepa, k'hamphani e lebeletse ho haha ​​​​sethala sa theknoloji sa RNA se ikhethang se ka atolosang phehello le halofo ea bophelo ba mekhoa e mecha ea phekolo ea RNA le ho li isa mefuteng e fapaneng ea lisele le lisele.

Mofuta o mocha oa phekolo ea RNA oa hlaha nakong ea histori

Ho tloha ka la 21 Tšitoe selemong sena, lebaleng la kalafo ea RNA, ho bile le liketsahalo tse 31 tsa pele tsa lichelete (bona mokhoa o qetellong ea sengoloa bakeng sa lintlha), tse kenyelletsang lik'hamphani tse 30 tsa maemo a holimo (k'hamphani e le 'ngoe e fumane chelete habeli), ka kakaretso ea lichelete tsa liranta tse limilione tse likete tse 1,74.Tlhahlobo ea lik'hamphani tsena e bontša hore bo-ramatsete ba na le tšepo e kholo mabapi le lik'hamphani tse tsoetseng pele tse lebelletsoeng ho rarolla mathata a mangata a kalafo ea RNA, e le ho hlokomela ka botlalo bokhoni ba kalafo ea RNA le ho thusa bakuli ba bangata.
'Me ho na le lik'hamphani tse ntseng li tsoela pele ho hlahisa mefuta e mecha ea phekolo ea RNA.Ho fapana le li-oligonucleotides tsa setso, RNAi kapa mRNA, mefuta e mecha ea limolek'hule tsa RNA tse entsoeng ke lik'hamphani tsena li lebelletsoe ho phunyeletsa botlolo ea liphekolo tse teng.
Circle RNA ke se seng sa libaka tse chesang haholo indastering.Ha ho bapisoa le linear mRNA, thekenoloji ea RNA e chitja e entsoeng ke k'hamphani ea morao-rao e bitsoang Orna Therapeutics e ka qoba ho tsejoa ke tsamaiso ea 'mele ea ho itšireletsa mafung le li-exonuclease, tse sa fokotseng haholo immunogenicity, empa hape li na le botsitso bo phahameng.Holim'a moo, ha ho bapisoa le linear RNA, conformation e mennweng ea RNA e chitja e nyane, mme RNA e chitja e ngata e ka jarisoa ka LNP e ts'oanang, ho ntlafatsa katleho ea phepelo ea kalafo ea RNA.Likarolo tsena li ka thusa ho ntlafatsa matla le ho tšoarella ha litlhare tsa RNA.
Selemong sena, k'hamphani e phethetse lichelete tsa US $221 milione Series B ea lichelete, hape e fihletse lipatlisiso letšebelisano ea nts'etsopele le Merck e fihlang ho US $ 3.5 bilione.Ntle le moo, Orna e boetse e sebelisa RNA e chitja ho hlahisa kalafo ea CAR-T ka kotloloho ho liphoofolo, ho tlatsa bopaki bamohopolo.
Ntle le RNA e chitja, theknoloji ea ho ikamahanya le eona ea mRNA (samRNAs) le eona e ratoa ke bo-ramatsete.Theknoloji ena e ipapisitse le mokhoa oa ho iphahamisa oa livaerase tsa RNA, tse ka susumetsang phetisetso ea tatellano ea samRNA ho cytoplasm, e lelefatsa polelo ea kinetics ea therapeutics ea mRNA, ka hona e fokotsa khafetsa tsamaiso.Ha ho bapisoa le li-mRNA tse tloaelehileng, samRNA e khona ho boloka maemo a tšoanang a protheine ka makhetlo a ka bang 10 a tlase.Selemong sena, RNAimmune, e shebaneng le nts'etsopele ea tšimo ena, e amohetse US $ 27 milione ka lichelete tsa Series A.
Theknoloji ea tRNA le eona e bohlokoa ho lebella.Phekolo e thehiloeng ho tRNA e ka "hlokomoloha" codon e fosahetseng ea ho emisa ha sele e etsa protheine, e le hore protheine e tloaelehileng ea bolelele bo felletseng e hlahisoe.Hobane ho na le mefuta e fokolang haholo ea li-stop codons ho feta mafu a amanang le eona, phekolo ea tRNA e na le monyetla oa ho hlahisa phekolo e le 'ngoe e ka phekolang maloetse a mangata.Selemong sena, hC Bioscience, e shebaneng le phekolo ea tRNA, e phahamisitse kakaretso ea US$40 milione ho lichelete tsa Series A.

Epilogue

E le mohlala oa phekolo o hlahang, phekolo ea RNA e fihletse tsoelo-pele e potlakileng lilemong tsa morao tjena, 'me liphekolo tse ngata li amohetsoe.Ho tsoa lits'ebetsong tsa morao-rao tsa indasteri, ho ka bonoa hore mekhoa ea phekolo ea RNA e ntse e atolosa mefuta e mengata ea maloetse ao mekhoa e joalo ea phekolo e ka e phekolang, ho hlōla litšitiso tse fapa-fapaneng tsa ho fana ka sepheo, le ho hlahisa limolek'hule tse ncha tsa RNA ho hlōla mefokolo ea mekhoa ea phekolo e teng mabapi le katleho le ho tšoarella.mathata a mangata.Nakong ena e ncha ea phekolo ea RNA, lik'hamphani tsena tse tsoetseng pele li ka fetoha sepheo sa indasteri lilemong tse 'maloa tse tlang.

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