Ina so in fara da tunatarwa wadda galibi ake rasawa a tattaunawar jama'a: Allurar rigakafin Covid mRNA sabbin kayayyaki ne na likitanci.
Kafin a ba da izinin gaggawa a shekarar 2020, ba a taɓa amfani da fasahar allurar rigakafin mRNA a cikin mutane ba. Gwaje-gwaje biyu na asibiti kawai, ɗaya daga Pfizer-BioNTech da ɗaya daga Moderna, sun taɓa gwada wannan dandamali a cikin mutane. Gabaɗaya, kimanin mutane 37,000 ne suka taɓa samun allurar rigakafin mRNA a tarihin magani (ban da ƙwarewar da ta gabata da allurar rigakafin cutar rabies, CMV, da ciwon daji waɗanda aka iyakance ga ƙananan nazarin farko). Wannan ba zargi ba ne; kawai magana ce ta gaskiya. Amma yana nufin cewa an fahimci yanayin aminci na dogon lokaci na waɗannan samfuran, kuma har yanzu, ba a fahimce su ba.
Abin da ke tafe ya saba wa kusan dukkan masana kimiyyar kwayoyin halitta. Yana da rikitarwa amma ina ƙoƙarin sauƙaƙe shi idan aka yi la'akari da ƙalubalen da ke tattare da shi. Yana da mahimmanci a tsara tsarin kwayoyin ga kowa da kowa domin yadda ake yin waɗannan alluran rigakafi kai tsaye ne ke tantance abin da ke cikin kwalbar.. Kuma abin da ke cikin kwalbar, da zarar an yi masa allura, zai yi yawo a cikin jiki kuma ya kunna tarin abubuwan da za su iya haifar da illa ga lafiya na dogon lokaci.
Rubutun In Vitro Ba Cikakkun Bayanan Masana'antu Ba Ne Kawai
Ana samar da alluran rigakafin mRNA da aka gyara ta amfani da tsari da ake kira in vitro transcription (IVT))IVT ita ce hanyar da ake amfani da ita wajen haɗa mRNA da aka gyara wanda a ƙarshe ya zama sinadari mai aiki a cikin allurar.
Wannan ba ƙaramin fasaha ba ne. IVT ta ginu ne bisa ga tsarin kwayoyin halitta na samfurin ƙarshe.
Masana kimiyya a BioNTech, gami da waɗanda ke da hannu kai tsaye wajen samar da allurar rigakafin Pfizer, sun buga cikakken bayani1 yana bayanin yadda amsawar IVT ba wai kawai ke samar da mRNA mai tsayi da aka yi niyya ba, har ma da nau'ikan samfuran da ba su da tsabta, yadda ake cire waɗannan yawanci, da kuma sakamakonsu na halitta idan suka ci gaba. Waɗannan umarnin kera tare da samfuran da suka ƙirƙira an kuma bayyana su dalla-dalla ta Moderna a cikin haƙƙin mallaka (US10,653,712 B2 da US10,077,439 B2). Amma mafi mahimmanci, wannan ilimin halittar kwayoyin halitta an kafa shi sosai tun kafin Covid. Babu ɗayan wannan da ake tsammani.
Kayan Farko: Samfuran DNA
A cikin zuciyarsa, amsawar IVT tana farawa da DNA mai layi biyu wanda ke samar da furotin da ake so. A wannan yanayin, furotin mai girma na SARS-CoV-2.
Tsarin shigar da ƙwayoyin cuta a cikin alluran rigakafin mRNA shine gyare gyare-gyare don inganta kwanciyar hankali da juriya ga ƙwayoyin halitta, gami da maye gurbin amino acid guda biyu waɗanda ke bambanta shi da karuwar ƙwayoyin cuta. Wannan gyaran an yi shi ne don inganta kwanciyar hankali da juriya ga ƙwayoyin cuta. ganganci.
Samfurin DNA da kansa zai iya ɗaukar siffofi daban-daban. A lokacin gwajin asibiti na farko na Pfizer, an yi amfani da gutsuttsuran DNA da PCR ta samar. Duk da haka, tsarin kera kayayyaki na kasuwanci ya dogara ne akan DNA da aka samo daga plasmids. Wannan yana da mahimmanci saboda plasmids suna ɗauke da ƙarin jerin ƙa'idodi. A yanayin Pfizer, waɗannan sun haɗa da abubuwa kamar SV40 promoter da jerin ori, waɗanda ke haifar da damuwa ko za su shiga ƙwayoyin ɗan adam.
Da zarar an ƙara wannan samfurin DNA zuwa ga amsawar IVT, tare da RNA polymerase da sauran abubuwan haɗin, ana canza shi zuwa mRNA (Hoto na 1).
IVT Tana Samar da Kayayyaki ta Tsarin Zane
Duk da cewa fitowar IVT da ake so ta samfurin mRNA mai cikakken tsayi ne, ainihin fitowar ta fi rikitarwa. Waɗannan sun haɗa da samfuran da suka biyo baya daban-daban a cikin nau'in (1) nau'ikan RNA daban-daban gami da RNA mai layi biyu (dsRNA), (2) DNA da aka haɗa da RNA (haɗaɗɗun RNA-DNA), da kuma (3) DNA kyauta daga samfurin asali (Hoto na 2).
Samar da waɗannan samfuran an rubuta su sosai kuma ba makawa, shi ya sa tsarkakewar ƙasa take da matuƙar muhimmanci ga aminci.
Hoto na 2. Kayayyakin da suka lalace da gurɓatattun abubuwan da ke tattare da ƙera IVT. An daidaita hoton daga 1.
Tsarkakewa Yana da Iyakoki da Aka Sani
Bayan ƙera, akwai matakai biyu na tsarkakewa da ake buƙata don fara cire DNA sannan a cire samfuran RNA (Hoto na 3):
Hoto na 3. Cire samfurin IVT. An daidaita hoton daga 2.
Domin cire DNA, ana ƙara wani enzyme a cikin cakuda amsawar da ake kira DNase I, wanda aka saba amfani da shi don lalata DNA mai gurɓatawa. Duk da cewa DNase I yana da tasiri akan DNA samfurin kyauta, bincike da yawa, gami da aikin da masana kimiyyar BioNTech kansu suka yi, sun nuna cewa DNase I ba shi da tasiri wajen cire DNA da aka haɗa da RNA (haɗaɗɗun RNA-DNA).
Wannan iyakancewa ba ta da ce-ce-ku-ce. An rubuta ta a cikin littattafai.
Abin da Nazarin Masu Zaman Kansu Ya Nuna
Wannan mahallin yana da matuƙar muhimmanci wajen fassara binciken da aka yi kwanan nan kan ƙwayoyin allurar riga-kafi da aka gama.
Masu bincike3 da masu kula da4 sun bayar da rahoton gano gurɓatattun DNA a cikin kowace kwalba da aka gwada. Waɗannan gurɓatattun sun haɗa da DNA mai nau'i biyu da kuma RNA-DNA hybrids waɗanda suka yi kama da suna da juriya ga narkewar DNase I.
A wasu samfurori, DNA mai ɓoye ƙwayoyin cuta yana nan a matakan da suka fi ninki 100 fiye da sauran jerin ƙwayoyin cuta na plasmid.5, yana nuna rashin daidaituwa ko rashin cika narkewar abinci. Binciken PCR na jeri da adadi ya ƙara gano gutsuttsuran DNA waɗanda suka kai matsakaicin tsayin ~ nau'i-nau'i 200, tare da wasu sun wuce kilobases 4. A lokuta da dama, an lura da jerin da suka mamaye kusan dukkan plasmid ɗin.
Idan aka haɗa waɗannan binciken, waɗannan binciken sun haifar da tambayoyi masu mahimmanci game da daidaito da cikar tsarkakewa yayin manyan masana'antu, da kuma game da illolin da ke tattare da ragowar ƙwayoyin nucleic acid a cikin mutane.
Dalilin da Yasa Gurɓatattun Acid Na Nucleic Suke Da Muhimmanci A Fannin Halittu
RNA da DNA suna da ƙarfi wajen kunna hanyoyin garkuwar jiki na asali. Wannan ba hasashe ba ne. Masu karɓar gane tsari da hanyar cGAS-STING suna mayar da martani sosai ga ƙwayoyin nucleic na ƙasashen waje, suna haifar da kumburi, hana girma, har ma da mutuwar ƙwayoyin halitta.
Waɗannan hanyoyin ne ainihin dalilin da ya sa ake sanya ido sosai kan kayayyakin maganin kwayoyin halitta.
Abin mamaki, an tsara alluran rigakafin Covid mRNA da gyare-gyare musamman don rage wannan ƙarfin kunna garkuwar jiki. Amma ƙwayoyin halittar RNA-DNA da gutsuttsuran DNA za su ci gaba da haifar da ƙarfin martanin garkuwar jiki duk da waɗannan gyare-gyaren.
Nacewa Ya Tada Sabbin Tambayoyi
Yanzu akwai shaidu masu yawa da ke nuna cewa karuwar mRNA da furotin na ci gaba da kasancewa a cikin kyallen jikin ɗan adam na tsawon makonni, watanni, har ma shekaru bayan allurar riga-kafi (Tebur 1).
Har yanzu ba mu san ko wannan juriyar tana nuna tsawon lokacin da aka ɗauka ana amfani da mRNA ba, ci gaba da fassara, ko hanyoyin da suka dogara da DNA. Amma idan aka yi la'akari da yuwuwar haɗakar DNA, da kuma DNA ɗin plasmid wanda ba a haɗa shi ba na tsawon lokaci a cikin ƙwayoyin tsoka,6 Ba abin mamaki ba ne a ɗauka cewa juriyar Spike mRNA, furotin, da ƙwayoyin rigakafi ga Spike shekaru bayan allurar riga-kafi ba shi da alaƙa da ƙazanta da samfuran DNA bayan IVT.
Tebur 1. Ƙaruwar mRNA da juriyar furotin bayan allurar rigakafi ga mutane
Tasirin Tsaro na Gajere da Na Dogon Lokaci
Idan aka haɗa waɗannan bayanai, za a iya ɗaukar wasu muhimman abubuwan da suka shafi tsaro.
Da farko, an bayar da rahoton mummunan martanin garkuwar jiki, gami da guguwar cytokine da kuma anaphylaxis, nan da nan bayan allurar riga-kafi. Bai kamata a yi watsi da irin waɗannan martanin kumburi kai tsaye a matsayin waɗanda ba su da alaƙa da ƙazanta, musamman idan aka yi la'akari da abin da aka sani game da kunna garkuwar jiki da nucleic-acid ke haifarwa.
Na biyu, kuma mafi mahimmanci, haɗari ne na dogon lokaci. Ci gaba da bayyana ƙarar na iya haifar da cututtukan garkuwar jiki na yau da kullun. Abin da ya fi damuwa shi ne yiwuwar haɗakar DNA, wanda ke ɗauke da haɗarin maye gurbi ko rushewar kwayoyin halitta. Wannan yana nufin haɗarin kamuwa da cutar kansa ko lahani na ci gaba ya danganta da inda da kuma shekarun da aka haɗa DNA ɗin.
Abin lura shi ne, FDA da kanta ta bayyana a cikin takardun bayananta cewa waɗannan alluran rigakafin ba su yi ba an tantance shi don kamuwa da cutar kansa (samuwar cutar kansa) ko gubar kwayoyin halitta (lalacewar DNA), wani batu da za a yi amfani da shi akai-akai kuma ana sa ran zai kasance a cikin kulawar maganin kwayoyin halitta, inda sa ido na dogon lokaci ya zama daidaitacce.
Gibin da ke tsakanin DNA a cikin allurar rigakafi ta mRNA
Tunda babu wata jayayya cewa akwai ragowar DNA a cikin alluran rigakafin mRNA, batun shine ko jagororin yanzu da iyakokin aminci sun dace da alluran rigakafin mRNA. An tabbatar mana cewa samfuran DNA suna cikin iyakokin da aka tsara a cikin jagororin ƙa'ida. To menene jagorar FDA game da samfuran DNA da gurɓatattun abubuwa?
An ƙirƙiro jagorar FDA mafi yawan amfani da ita kan ragowar DNA (≤10 ng a kowace allura) don allurar rigakafin ƙwayoyin cuta da aka samar a cikin ƙwayoyin halitta masu rai waɗanda suka rabu kuma suka “tsirara,” tare da iyakataccen ikon shiga ƙwayoyin halittar ɗan adam. Duk da haka, ba a samar da allurar rigakafin mRNA a cikin ƙwayoyin halitta ba, ragowar DNA ɗinsu ba a samo shi daga ƙwayoyin halitta ba, kuma mafi mahimmanci, DNA a cikin allurar rigakafin mRNA ba tsirara ba ne. Yana da alaƙa da tsarin isar da LNP, wanda ke sauƙaƙa wa DNA shiga cikin ƙwayoyin halitta. Jagorar FDA ta 2010 a bayyane take cewa ba ta kafa iyaka mai dacewa ga DNA da ke da alaƙa da samfuran LNP ba.
Sauran jagorar da aka fi ambata ita ce daga WHO don maganin furotin da aka sake haɗawa waɗanda ke magance ragowar DNA a cikin samfuran kamar ƙwayoyin rigakafi na monoclonal ko hormones da aka samar a cikin ƙwayoyin halitta. A nan kuma, ragowar DNA ya samo asali ne daga ƙwayoyin masu masaukin baki ko plasmids na bayyanawa, yana nan a matsayin alama, DNA mara ɓoyewa (tsirara), kuma samfurin ƙarshe shine furotin mai tsarkakewa, ba maganin da ke tushen nucleic acid ba (alurar mRNA). Don haka wannan jagorar ba ta shafi alluran mRNA ba.
Ba a ambaci ƙa'idodin FDA ko WHO da aka fi ambata don ragowar DNA ba an haɓaka shi don alluran rigakafin mRNA, kuma ba sa magance wannan matsalar tsaro kai tsaye.
Abin da WHO ta ce game da allurar rigakafin mRNA - Bayan An Yi Amfani da su
A shekarar 2022, Hukumar Lafiya ta Duniya ta fitar da wata jagora ta musamman game da alluran rigakafin mRNA7Abin lura shi ne, an fitar da wannan takarda bayan Ya bayyana musamman cewa wannan jagorar ta mayar da martani ne ga:batutuwan tsaro, samarwa da kuma dokoki da suka shafi wannan sabuwar fasaha."Takardar ta kuma yi wasu muhimman bayanai:
"Saboda ba a samu cikakken bayani game da hanyoyin da ake amfani da su don samarwa ba tukuna, ba a daidaita ka'idojin sarrafawa don alluran rigakafin mRNA masu aminci da inganci ba, kuma wasu cikakkun bayanai sun kasance mallakar mallakarsu don haka ba a samun su a bainar jama'a ba, ba zai yiwu a samar da takamaiman jagororin ƙasa da ƙasa ko shawarwari a wannan lokacin ba."
Har ila yau yana cewa: "Cikakkun hanyoyin samarwa da sarrafawa…ya kamata a tattauna su kuma a amince da su ta Hukumar Kula da Kayayyakin Kasa (NRA)] bisa ga kowane hali."
Hukumar Lafiya ta Duniya (WHO) ta amince cewa ba a daidaita tsarin kula da alluran rigakafin mRNA ba tukuna kuma ba zai yiwu a kafa takamaiman jagororin ƙasa da ƙasa ko shawarwari ba. Bugu da ƙari, ana buƙatar sa ido kan ƙa'idoji don tantancewa daga hukumomin ƙasa.
An bayyana hakan ne bayan an yi amfani da allurar rigakafin mRNA..
Kuma har zuwa lokacin rubuta wannan Substack, FDA har yanzu ba ta kafa ƙa'idodi na yau da kullun don alluran rigakafin mRNA ba kuma ta samar da wata shaida da bayanai masu tushen aminci don tallafawa duk wani iyaka na DNA a cikin alluran rigakafin mRNA.
A ƙarshe, ya kamata a maimaita: yayin da fasahar mRNA ba sabuwa ba ce, kafin Covid, an tsara ta ne a matsayin maganin kwayoyin halitta, ba a matsayin allurar rigakafi ta gargajiya ba. Matsalolin aminci da ke tattare da samfuran DNA da ke cikin allurar rigakafin Covid za su kasance iri ɗaya da kowace allurar rigakafin mRNA, gami da waɗanda ke maganin mura, RSV, ko ma allurar rigakafin mRNA don ciwon daji.
Wannan saboda samfuran mRNA sun bambanta sosai. Dole ne su shiga ƙwayoyin halitta su kuma umarce su da su samar da furotin na ƙasashen waje. Wannan ba kamar sauran alluran rigakafi na gargajiya ba ne waɗanda ke isar da furotin kai tsaye. Babu wani misali na asibiti ga wannan dandamali, kuma babu wani misali na asibiti don maimaita allurar. Kuma tabbas babu wani misali a yawan jama'a.
A wannan matakin, ba tare da wata annoba ba, tarin bayanai na injiniya da kuma lura da asibiti, da kuma yaduwar kayayyakin allurar rigakafin mRNA da ke shigowa kasuwa, muna buƙatar bayyana gaskiya da kuma yin aiki kai tsaye tare da nazarin tsaro mai mahimmanci daga masu kula da lafiya, musamman FDA da ke kafa muhimman jagororin ƙera waɗannan samfuran - musamman dangane da samfuran DNA da suka fito daga cikinsu.
Sabbin fasahohi suna buƙatar sabon bincike - ba shiru, hasken gas, ko takunkumi ba.
References
1 https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1426129/full
2 Webb C, Ip S, da sauransu Mol Pharm. Afrilu 4, 2022;19(4):1047-1058. doi: 10.1021/
3 https://www.tandfonline.com/doi/10.1080/08916934.2025.2551517?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
4 https://www.tga.gov.au/resources/publication/tga-laboratory-testing-reports/summary-report-residual-dna-and-endotoxin-covid-19-mrna-vaccines-conducted-tga-laboratories.
5 https://zenodo.org/records/17832183; https://www.scstatehouse.gov/CommitteeInfo/SenateMedicalAffairsCommittee/PandemicPreparedness/Phillip-Buckhaults-SC-Senate-09122023-final.pdf
6 Wang et al. (2004) – “Gano haɗakar DNA ta plasmid cikin DNA ta plasmid bayan allurar ciki da kuma electroporation” (Gene Therapy, 2004). A cikin beraye, an yi wa DNA ta plasmid tsirara allura ta cikin jijiya, sannan aka biyo baya da electroporation don haɓaka sha. Ta amfani da PCR mai matuƙar tasiri akan DNA ta genomic mai tsabta (tare da rabuwar gel don cire siffofin extrachromosomal), marubutan sun gano abubuwan haɗin kai guda huɗu masu zaman kansu a makonni 4 bayan allurar. Jerin mahaɗin ya tabbatar da wuraren haɗin kai bazuwar (babu wuraren da suka fi so), daidai da haɗin ƙarshen da ba na homologue ba. Mitar haɗin kai ya yi ƙasa amma ana iya aunawa. Wannan shine ɗayan mafi bayyanannun nuni na ainihin abubuwan haɗin kai na bazata a cikin jiki don DNA ta plasmid tsirara a cikin tsoka. Abin lura - wannan binciken ya yi amfani da ingantaccen isar da DNA ta hanyar electroporation wanda mutum zai iya kwatantawa da ingantaccen isarwa ta hanyar LNPs.
Martin et al. (1999) – “Alluran rigakafin cutar malaria ta Plasmid DNA: Yiwuwar Haɗakar Kwayoyin Halitta bayan Allurar Jijiyoyin Jiki” (Maganin Halittar Dan Adam). Wannan binciken da aka yi a baya ya gwada plasmid DNA IM a cikin beraye kuma ya yi amfani da Southern blot hybridization da PCR akan DNA genomic mai nauyin ƙwayoyin halitta don bincika haɗin kai. Duk da cewa juriya galibi ba ta cikin ƙwayoyin halitta ba ce, sun ba da rahoton shaidar da ke nuna haɗin kai mai wuya a wasu samfuran (kodayake ba a tsara shi daidai kamar yadda aka tsara shi daga baya ba). Ya kafa ma'auni don ƙarancin haɗari amma ya amince da yuwuwar aukuwar ƙananan mitoci, yana tasiri ga jagorar FDA ta gaba kan allurar rigakafin DNA.
Ledwith et al. (2000) – “Alluran rigakafin DNA na plasma: Binciken haɗakar DNA ta ƙwayoyin halitta bayan allurar intramuscular a cikin beraye” (Intervirology). An nuna cewa DNA ɗin plasmid tsirara da aka yi wa allurar IM a cikin beraye kuma duk da cewa ba a ga haɗin kai da za a iya ganowa ba, har yanzu an gano DNA a cikin tsokar quadriceps har zuwa makonni 26. DNA ɗin ya kasance ba ya cikin chromosomes.
7 Kwamitin Ƙwararru na WHO kan Daidaita Halittu Rahoton 74 na Shafi na 3. Kimanta inganci, aminci da ingancin alluran rigakafin RNA na manzo don rigakafin cututtuka masu yaɗuwa: la'akari da ƙa'idoji https://cdn.who.int/media/docs/default-source/biologicals/vaccine-standardization/annex-3—mrna-vaccines_who_trs_1039_web-2.pdf
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Dokta Charlotte Kuperwasser fitaccen Farfesa ne a Sashen Ci gaba, Kwayoyin Halitta, da Kimiyyar Halittu a Makarantar Magunguna ta Jami'ar Tufts da kuma Daraktan Tufts Convergence Laboratory a Tufts. Dr. Kuperwasser an santa a duniya don ƙwarewarta a ilimin halittar mahaifa da ciwon nono, da rigakafi. Ita mamba ce a kwamitin ba da shawara kan ayyukan rigakafi.
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