Source: WuXi AppTec

Shekarun baya-bayan nan, fannin jiyya na RNA ya nuna yanayin fashe-fashe.a cikin shekaru 5 da suka gabata kadai, FDA ta amince da magungunan RNA guda 11, kuma wannan adadin har ma ya zarce jimillar jimillar magungunan RNA da aka amince da su a baya!Idan aka kwatanta da magungunan gargajiya, jiyya na RNA na iya haɓaka hanyoyin kwantar da hankali da sauri tare da ƙimar nasara mafi girma muddin an san jerin abubuwan da aka yi niyya.A gefe guda, yawancin hanyoyin kwantar da hankali na RNA har yanzu suna samuwa ne kawai don magance cututtukan da ba kasafai ba, kuma ci gaban irin waɗannan hanyoyin kwantar da hankali har yanzu yana fuskantar ƙalubale da yawa dangane da dorewar jiyya, aminci, da bayarwa.A cikin labarin yau, daTawagar abun ciki na WuXi AppTec za ta yi nazari kan ci gaban da aka samu a fannin jiyya na RNA a shekarar da ta gabata, kuma za ta sa ido ga makomar wannan filin da ya fito tare da masu karatu.

▲ Magungunan RNA guda 11 ko alluran rigakafin da FDA ta amince dasu a cikin shekaru 5 da suka gabata

Daga cututtuka masu wuya zuwa cututtuka na kowa, ƙarin furanni suna fure

A cikin sabuwar annoba ta kambi, an haifi rigakafin mRNA daga wani wuri kuma ya sami kulawa sosai daga masana'antu.Bayan danasara wajen samar da alluran rigakafin cututtuka, wani babban kalubalen da ke fuskantar fasahar mRNA shine fadada iyakokin aikace-aikace don magani da rigakafin wasu cututtuka.
Tsakanin su,allurar rigakafin cutar kansa wani muhimmin filin aikace-aikace na fasahar mRNA, kuma mun ga sakamako mai kyau na asibiti na allurar cutar kansa da yawa a wannan shekara.A wannan watan, maganin cutar kansa na mutum ɗaya wanda Moderna da Merck suka haɓaka tare da mai hana PD-1 Keytruda,rage hadarinna sake dawowa ko mutuwa a cikin marasa lafiya tare da mataki na III da IV melanoma bayan cikakken maganin ƙwayar cuta ta hanyar 44% (idan aka kwatanta da Keytruda monotherapy).Sanarwar da manema labarai ta fitar ta nuna cewa wannan shi ne karo na farko da allurar cutar kansar mRNA ta nuna inganci a cikin maganin cutar sankarau a cikin gwajin asibiti da aka yi bazuwar, wanda wani lamari ne mai ban mamaki a ci gaban rigakafin cutar kansar mRNA.
Bugu da kari, allurar rigakafin mRNA kuma na iya haɓaka tasirin jiyya na maganin tantanin halitta.Misali, wani binciken da BioNTech ya yi ya nuna cewa idan an fara ba marasa lafiya da ƙaramin adadin maganin CAR-T da aka yi niyya na CLDN6.Saukewa: BNT211, sannan aka yi musu allurar rigakafin mRNA da ke ɓoye CLDN6, za su iya motsa ƙwayoyin CAR-T a cikin vivo ta hanyar bayyana CLDN6 akan saman sel masu gabatar da antigen.Amplification, don haka inganta tasirin anticancer.Sakamakon farko ya nuna cewa 4 daga cikin 5 marasa lafiya da suka karbi maganin haɗin gwiwa sun sami amsa na ɓangare, ko 80%.

Baya ga maganin mRNA, oligonucleotide therapy da RNAi far sun kuma sami sakamako mai kyau wajen faɗaɗa iyakokin cututtuka.A cikin maganin ciwon hanta na kullum, kusan kashi 30% na marasa lafiya ba za su iya gano antigen na Hepatitis B da kwayar cutar hepatitis B a cikin vivo bayan amfani da maganin antisense oligonucleotide.bepirovirsen tare da GSK da Ionis suka haɓakana makonni 24.A wasu marasa lafiya, ko da makonni 24 bayan dakatar da jiyya, waɗannan alamun cutar hanta B har yanzu ba a iya gano su a cikin jiki.
Kwatsam, maganin RNAiVIR-2218 tare da haɗin gwiwar Vir Biotechnology da Alnylam an haɗa sutare da interferon α, kuma a cikin gwaji na asibiti na lokaci na 2, kusan kashi 30% na marasa lafiya na hepatitis B na kullum sun kasa gano cutar hanta ta B surface antigen (HBsAg).Bugu da ƙari, waɗannan marasa lafiya sun haɓaka ƙwayoyin rigakafi a kan furotin na hepatitis B, suna nuna kyakkyawar amsawar tsarin rigakafi.Dauke waɗannan sakamakon tare, masana'antun sun nuna cewa maganin RNA na iya zama mabuɗin maganin aikin hanta na hepatitis B.
Wannan na iya zama farkon jiyya na RNA don cututtukan gama gari.A cewar bututun R&D na Alnylam, yana kuma haɓaka hanyoyin kwantar da hankali na RNAi don maganin hauhawar jini, cutar Alzheimer, da steatohepatitis marasa giya, kuma nan gaba yana da daraja.

Watsawa cikin ƙulli na isar da jiyya na RNA

Isar da maganin RNA yana ɗaya daga cikin ƙullun da ke iyakance aikace-aikacen sa.Masana kimiyya kuma suna haɓaka fasahohi iri-iri don isar da maganin RNA na musamman ga gabobin jiki da kyallen takarda ban da hanta.
Ɗayan yuwuwar hanyoyin ita ce “daure” RNAs na warkewa tare da takamaiman ƙwayoyin nama.Misali, Avidity Biosciences kwanan nan ya sanar da cewa dandamalin fasahar sa na iya haɗa ƙwayoyin rigakafi na monoclonal zuwa oligonucleotides zuwadaure siRNA yadda ya kamata.aika zuwa kwarangwal tsoka.Sanarwar da aka fitar ta yi nuni da cewa, wannan shi ne karo na farko da ake samun nasarar kai wa siRNA hari da kuma isar da shi ga tsokar tsokar dan Adam, wanda hakan ya kasance babban ci gaba a fagen maganin RNA.

Tushen hoto: 123RF

Baya ga fasahar haɗin gwiwar antibody, kamfanoni da yawa masu haɓaka nanoparticles na lipid (LNP) suma suna “inganta” irin waɗannan dillalai.Misali, Sake Code Therapeuticyana amfani da fasaha ta musamman na Zaɓin Ƙwararrun Ƙwararrun Ƙwararrun LNP (SORT) don sadar da nau'o'in nau'in maganin RNA iri-iri zuwa ga huhu, sabulu, hanta da sauran gabobin.A wannan shekarar, kamfanin ya sanar da kammala shirin bada tallafin dalar Amurka miliyan 200 na jerin B, tare da manyan sassan Pfizer, Bayer, Amgen, Sanofi da sauran manyan kamfanonin harhada magunguna sun shiga cikin jarin.Kernal Biologics , wanda kuma ya karbi dala miliyan 25 a cikin jerin kudade na A wannan shekara, kuma yana haɓaka LNPs waɗanda ba sa tarawa a cikin hanta, amma zasu iya sadar da mRNA zuwa ƙwayoyin cuta irin su kwakwalwa ko takamaiman ciwace-ciwacen daji.
Orbital Therapeutics , wanda aka yi muhawara a wannan shekara, kuma yana ɗaukar isar da maganin RNA a matsayin babban jagorar ci gaba.Ta hanyar haɗa fasahar RNA da hanyoyin isarwa, kamfanin yana tsammanin gina wani dandamali na fasaha na RNA na musamman wanda zai iya tsawaita tsayin daka da rabin rayuwar sabbin hanyoyin kwantar da hankali na RNA tare da isar da su zuwa nau'ikan tantanin halitta da nama daban-daban.

Wani sabon nau'in maganin RNA ya fito a lokacin tarihi

Ya zuwa ranar 21 ga Disamba na wannan shekara, a fagen jiyya na RNA, an sami 31 abubuwan bayar da kudade na farko (duba tsarin a ƙarshen labarin don cikakkun bayanai), wanda ya haɗa da kamfanoni masu yanke hukunci 30 (kamfani ɗaya ya karɓi kuɗi sau biyu), tare da jimlar kuɗin dalar Amurka biliyan 1.74.Binciken waɗannan kamfanoni ya nuna cewa masu saka hannun jari sun fi kwarin gwiwa game da waɗancan kamfanonin da ake sa ran za su warware ƙalubalen da yawa na maganin RNA, don samun cikakkiyar fahimtar yuwuwar maganin RNA da kuma amfana da ƙarin marasa lafiya.
Kuma akwai kamfanoni masu tasowa masu tasowa waɗanda ke haɓaka sabbin nau'ikan magungunan RNA gaba ɗaya.Ba kamar na al'ada oligonucleotides, RNAi ko mRNA, sabbin nau'ikan kwayoyin RNA da waɗannan kamfanoni suka haɓaka ana tsammanin za su shiga cikin kuncin hanyoyin da ake amfani da su.
Madauwari RNA tana ɗaya daga cikin wurare masu zafi a cikin masana'antar.Idan aka kwatanta da mRNA na layi, fasahar RNA madauwari da wani kamfani mai suna Orna Therapeutics ya ƙera zai iya guje wa gane shi ta hanyar tsarin rigakafi na halitta da exonucleases, wanda ba kawai yana rage yawan rigakafi ba, amma kuma yana da kwanciyar hankali.Bugu da ƙari, idan aka kwatanta da RNA na layi, nau'in nau'in RNA na madauwari yana ƙarami, kuma ƙarin madauwari RNA za a iya lodawa tare da LNP iri ɗaya, inganta ingantaccen isar da jiyya na RNA.Waɗannan fasalulluka na iya taimakawa haɓaka ƙarfi da dorewar magungunan RNA.
A wannan shekara, kamfanin ya kammala zagaye na tallafin dala miliyan 221 na jerin B, kuma ya kai ga bincike daHaɗin gwiwar haɓaka tare da Merck har zuwa dalar Amurka biliyan 3.5.Bugu da ƙari, Orna kuma yana amfani da RNA madauwari don samar da maganin CAR-T kai tsaye a cikin dabbobi, yana kammala tabbacin.ra'ayi.
Baya ga RNA madauwari, fasahar mRNA (samRNAs) mai haɓaka kai kuma ta sami fifiko daga masu saka hannun jari.Wannan fasaha ta dogara ne akan tsarin ƙara girman kai na ƙwayoyin cuta na RNA, wanda zai iya haifar da maimaita tsarin samRNA a cikin cytoplasm, yana tsawaita maganan kinetics na magungunan mRNA, ta haka zai rage yawan gudanarwa.Idan aka kwatanta da mRNA na layi na gargajiya, samRNA yana iya kiyaye matakan furcin furotin iri ɗaya a kusan ƙananan allurai sau 10.A wannan shekara, RNAimmune, wanda ke mai da hankali kan ci gaban wannan filin, ya sami dalar Amurka miliyan 27 a cikin tallafin Series A.
Fasahar tRNA kuma tana da daraja.Maganin tushen tRNA na iya "kula da" codon tasha ba daidai ba lokacin da tantanin halitta ke yin furotin, ta yadda aka samar da furotin mai cikakken tsayi na al'ada.Saboda akwai ƙarancin nau'ikan codons na tsayawa fiye da cututtukan da ke da alaƙa, maganin tRNA yana da yuwuwar haɓaka jiyya ɗaya wanda zai iya magance cututtuka da yawa.A wannan shekara, hC Bioscience , wanda ke mai da hankali kan maganin tRNA, ya tara jimillar dalar Amurka miliyan 40 a cikin tallafin Series A.

Epilogue

A matsayin samfurin jiyya mai tasowa, maganin RNA ya sami ci gaba cikin sauri a cikin 'yan shekarun nan, kuma an yarda da yawancin hanyoyin kwantar da hankali.Daga sabbin abubuwan da suka faru a cikin masana'antar, ana iya ganin cewa manyan hanyoyin kwantar da hankali na RNA suna faɗaɗa nau'ikan cututtukan da irin waɗannan hanyoyin maganin za su iya magance su, da shawo kan ƙulla-ƙulla daban-daban a cikin isar da niyya, da haɓaka sabbin ƙwayoyin RNA don shawo kan iyakokin hanyoyin da ake amfani da su ta fuskar inganci da dorewa.kalubale masu yawa.A cikin wannan sabon zamanin jiyya na RNA, waɗannan manyan kamfanoni na iya zama abin da masana'antar ke mayar da hankali a kai a cikin ƴan shekaru masu zuwa.

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