Rashin ji (HL) ita ce mafi yawan cututtukan nakasa a ji a cikin mutane.A cikin kasashen da suka ci gaba, kusan kashi 80 cikin 100 na kurame da yara ke fama da su kafin yare suna faruwa ne ta dalilin kwayoyin halitta.Mafi yawanci sune lahani guda ɗaya (kamar yadda aka nuna a hoto na 1), an gano maye gurbi guda 124 da ke da alaƙa da asarar jin rashin jin daɗi a cikin ɗan adam, sauran kuma abubuwan muhalli ne ke haifar da su.Ƙwaƙwalwar ƙwayar cuta (na'urar lantarki da aka sanya a cikin kunnen ciki wanda ke ba da wutar lantarki kai tsaye zuwa jijiya mai ji) shine mafi nisa mafi kyawun zaɓi don magance HL mai tsanani, yayin da taimakon jin (na'urar lantarki ta waje wanda ke canzawa da haɓaka raƙuman sauti) zai iya taimakawa marasa lafiya tare da matsakaicin HL.Koyaya, a halin yanzu babu magunguna da ake da su don magance HL (GHL na gado).A cikin 'yan shekarun nan, maganin kwayoyin halitta ya sami ƙarin kulawa a matsayin hanya mai ban sha'awa don magance rashin aikin kunne na ciki.
Hoto 1.Rarraba nau'in bambancin da ke da alaƙa da kurma.[1]
Kwanan nan, masana kimiyya daga Cibiyar Salk da Jami'ar Sheffield sun buga sakamakon bincike a cikin Kwayoyin Farko - Hanyoyi & Ci gaban Clinical [2], wanda ya nuna fa'idar aikace-aikacen da za a iya amfani da shi a cikin vivo gene far na kurun gado.Uri Manor, mataimakin farfesa na bincike a Cibiyar Salk kuma darektan Cibiyar Waitt don Advanced Biophotonics, ya ce an haife shi da mummunan rashin ji kuma yana jin cewa maido da ji zai zama kyauta mai ban mamaki.Binciken da ya gabata ya gano cewa Eps8 shine furotin mai sarrafa actin tare da ɗaurin actin da ayyukan capping;a cikin sel gashi na cochlear, hadaddun furotin da Eps8 suka kirkira tare da MYO15A, WHIRLIN, GPSM2 da GNAI3 galibi suna wanzuwa a cikin mafi yawan Tukwici na dogon stereocilia, wanda tare da MYO15A suna gano BAIAP2L2 a cikin guntun stereocilia, ana buƙatar don kiyaye daurin gashi.Sabili da haka, Eps8 na iya daidaita tsawon stereocilia na sel gashi, wanda ke da mahimmanci ga aikin ji na yau da kullun;Goge Eps8 ko maye gurbi zai haifar da gajeriyar stereocilia, wanda ke sa ya kasa canza sauti yadda yakamata zuwa siginar lantarki don fahimtar kwakwalwa, wanda hakan ke haifar da kurma..A lokaci guda kuma, mai haɗin gwiwa Walter Marcotti, farfesa a Jami'ar Sheffield, ya gano cewa ƙwayoyin gashi ba za su iya ci gaba ba kullum idan babu Eps8.A cikin wannan binciken, Manor da Marcotti sun haɗu don bincika ko ƙara Eps8 zuwa sel na stereocilia zai iya dawo da aikin su kuma, bi da bi, inganta ji a cikin mice.Ƙungiyar binciken ta yi amfani da ƙwayar cuta mai alaƙa da adeno (AAV) vector Anc80L65 don sadar da jerin lambobin da ke dauke da nau'in daji EPS8 a cikin cochlea na Eps8-/- jariri P1-P2 mice ta hanyar allurar membrane ta zagaye;a cikin linzamin kwamfuta cochlear gashi Kwayoyin An gyara aikin stereocilia kafin su girma;kuma tasirin gyaran gyare-gyare ya kasance ta hanyar fasahar hoto da ma'auni na stereocilia.Sakamakon ya nuna cewa Eps8 ya ƙara tsawon stereocilia kuma ya dawo da aikin ƙwayar gashi a cikin ƙananan ƙananan ƙwayoyin cuta.Har ila yau, sun gano cewa, bayan lokaci, sel sun zama kamar sun rasa ikon ceton su ta wannan maganin kwayoyin halitta.Ma'anar ita ce wannan magani na iya buƙatar gudanar da shi a cikin mahaifa, kamar yadda Eps8-/- kwayoyin gashi na iya girma ko kuma sun tara lalacewa fiye da gyara bayan an haifi mice."Eps8 furotin ne mai ayyuka daban-daban, kuma har yanzu akwai abubuwa da yawa da za a bincika," in ji Manor.Bincike na gaba zai hada da binciken tasirin maganin Eps8 a cikin maido da ji a matakai daban-daban na ci gaba, da kuma ko zai yiwu a tsawaita damar jiyya.Ba zato ba tsammani, a cikin Nuwamba 2020, Farfesa KarenB Avraham na Jami'ar Tel Aviv a Isra'ila ya buga sakamakonsa a cikin mujallar EMBO Molecular Medicine [3], ta amfani da sabuwar fasahar maganin kwayoyin halitta don ƙirƙirar ƙwayar cuta mai alaƙa da adeno mai cutarwa AAV9-PHP.B, An gyara lahanin kwayoyin halitta a cikin kwayoyin gashi na Syne4-/- mice ta hanyar allurar kwayar cutar da ke dauke da jerin codeing na Syne4 a cikin kunnen ciki na mice, yana ba shi damar shiga cikin sel gashi kuma ya saki kayan da ke dauke da kwayoyin halitta, yana ba su damar girma kuma suyi aiki akai-akai (kamar yadda a cikin siffa 2).
Hoto2.Matsakaicin tsari na jikin kunne na ciki, tare da mai da hankali kan sashin Corti da aikin salula na nesprin-4.
Ana iya ganin cewa, yin amfani da maganin kwayoyin halitta don cimma manufar magance cututtukan da ake gada a matakin jinsin halittu ta hanyar sanyawa, cirewa ko gyara duk wani rikitattun kwayoyin halitta don magani (wato sarrafa canjin kwayoyin halittar cutar) yana da matukar tasiri a asibiti.aikace-aikace masu yiwuwa.Hanyoyin jiyya na kwayoyin halitta na yanzu don ƙarancin kurma za a iya raba su zuwa nau'ikan masu zuwa:
maye gurbin kwayoyin halitta
Maye gurbin kwayoyin halitta shine mafi "madaidaici" nau'i na maganin kwayoyin halitta, bisa ga ganowa da maye gurbin wani maras kyau tare da kwafi na al'ada ko nau'in daji na kwayar halitta.Nasarar farko na binciken maganin jiyya na cikin kunne don asarar ji wanda ya haifar da gogewar jigilar jigilar vesicular glutamate 3 (VGLUT3);Isar da tsaka-tsakin AAV1 na exogenous VGLUT3 wuce gona da iri a cikin sel gashi na kunne na ciki (IHCs) na iya haifar da ci gaba da dawo da ji, dawo da ilimin halittar jiki na ribbon, da martani mai girgiza [4].Duk da haka, a cikin misalan da suka haɗa da maye gurbin AAV guda biyu da aka ba da su a cikin gabatarwar da ke sama, yana da mahimmanci a lura cewa nau'ikan linzamin kwamfuta da aka yi amfani da su don wasu nau'o'in nau'in nau'in cutarwa na lalacewa na rashin jin daɗi na ɗan lokaci sun bambanta da mutane, kuma a cikin P1 mice , kunnen ciki yana cikin babban mataki na ci gaba.Akasin haka, an haifi ’yan Adam da babban kunne na ciki.Wannan bambance-bambancen yana hana yiwuwar amfani da sakamakon linzamin kwamfuta don maganin cututtukan kurma na gadon ɗan adam sai dai idan ba a isar da magungunan ƙwayoyin cuta ga kunnuwan linzamin kwamfuta ba.
Gyaran Halitta: CRISPR/Cas9
Idan aka kwatanta da "maye gurbin kwayoyin halitta", ci gaban fasahar gyaran kwayoyin halitta ya kawo wayewar maganin cututtukan kwayoyin halitta daga tushe.Mahimmanci, hanyar gyare-gyaren kwayoyin halitta ta haifar da gazawar hanyoyin maganin kwayoyin cutar wuce gona da iri na gargajiya wadanda ba su dace da manyan cututtukan kurame na gado ba, da kuma matsalar cewa hanyar wuce gona da iri ba ta dadewa.Bayan da masu binciken kasar Sin suka fitar da mutant allele na Myo6C442Y a cikin berayen Myo6WT/C442Y ta amfani da tsarin gyaran kwayoyin halittar AAV-SaCas9-KKH-Myo6-g2, kuma a cikin watanni 5 da bugun, berayen An dawo da aikin sauraron samfurin;A lokaci guda, an kuma lura da cewa an inganta yawan rayuwa na ƙwayoyin gashi a cikin kunnen ciki, siffar cilia ta zama na yau da kullum, kuma an gyara alamun electrophysiological [5].Wannan shi ne bincike na farko a duniya da aka yi amfani da fasahar CRISPR/Cas9 don maganin kurame na gado wanda maye gurbi na Myo6 ke haifarwa, kuma muhimmin ci gaba ne na bincike na fasahar gyara kwayoyin halitta don maganin kurma na gado.Fassarar magani na asibiti yana ba da ingantaccen tushen kimiyya.
Hanyoyin isar da kwayoyin halitta
Domin maganin kwayoyin halitta ya yi nasara, kwayoyin DNA tsirara ba za su iya shiga cikin sel yadda ya kamata ba saboda hydrophilicity da mummunan cajin ƙungiyoyin phosphate, kuma don tabbatar da amincin ƙwayoyin ƙwayoyin nucleic acid da aka haɓaka, dole ne a zaɓi hanya mai aminci da inganci.Ana isar da ƙarin DNA zuwa tantanin halitta ko nama.Ana amfani da AAV ko'ina azaman abin hawa na isarwa don maganin cututtuka saboda babban tasirin sa, ƙarancin rigakafi, da kuma yanayin zafi zuwa nau'ikan nama daban-daban.A halin yanzu, babban aikin bincike ya ƙayyade tropism na nau'i-nau'i daban-daban na AAV dangane da nau'in tantanin halitta daban-daban a cikin cochlea na linzamin kwamfuta.Yin amfani da halayen bayarwa na AAV da aka haɗe tare da masu tallata tantanin halitta na iya cimma takamaiman magana ta tantanin halitta, wanda zai iya rage tasirin kashe-kashe.Bugu da kari, a matsayin madadin na'urorin AAV na al'ada, ana ci gaba da haɓaka sabbin sifofin AAV na roba kuma suna nuna mafi girman ikon canzawa a cikin kunnen ciki, wanda AAV2/Anc80L65 shine mafi yawan amfani da su.Hanyoyin isar da kwayar cutar ba za a iya ƙara raba su zuwa hanyoyin jiki (microinjection da electroporation) da hanyoyin sinadarai (tushen lipid, tushen polymer, da nanoparticles na zinariya).Dukkan hanyoyin biyu an yi amfani da su wajen magance cututtukan kurma na gado kuma sun nuna fa'idodi da iyakancewa daban-daban.Baya ga abin hawa isarwa don jiyya a matsayin abin hawa, ana iya amfani da hanyoyi daban-daban don gudanar da tsarin halittar vivo dangane da nau'ikan tantanin halitta daban-daban, hanyoyin gudanarwa, da ingancin warkewa.Matsakaicin tsarin kunnuwa na ciki yana sa ya zama da wahala a kai ga sel da aka yi niyya kuma rarraba abubuwan gyara kwayoyin halitta yana jinkirin.Labyrinth membranous yana cikin kashin labyrinth na ƙashi na ɗan lokaci kuma ya haɗa da duct na cochlear, duct semicircular, utricle, da balloon.Keɓewar danginta, ƙarancin wurare dabam dabam na lymphatic, da rabuwa da jini ta hanyar shingen maze na jini yana iyakance ingantaccen isar da tsarin warkewa ga ƙananan berayen kawai.Don samun titers na ƙwayoyin cuta masu dacewa da maganin kwayoyin halitta, allurar kai tsaye ta gida na ƙwayoyin cuta a cikin kunnen ciki ya zama dole.Hanyoyin da aka kafa na allura sun haɗa da [6]: (1) membrane taga (RWM), (2) tracheostomy, (3) endolymphatic ko perilymphatic cochleostomy, (4) murfin taga zagaye da Tube feestration (CF) (kamar yadda yake a cikin siffa 3).
Hoto 3.Isar da kunnen ciki na maganin kwayoyin halitta.
Ko da yake an sami ci gaba da yawa a cikin ilimin halittar jini, bisa ga burin fassarar asibiti, ana buƙatar ƙarin aiki kafin maganin ƙwayoyin cuta ya zama zaɓi na farko na jiyya ga marasa lafiya da cututtukan ƙwayoyin cuta, musamman a cikin haɓaka amintattun ƙwayoyin cuta masu inganci da hanyar bayarwa.Amma mun yi imanin cewa nan gaba kaɗan, waɗannan nau'ikan jiyya za su zama jigon jiyya na musamman kuma za su yi tasiri sosai ga rayuwar mutanen da ke da cututtukan ƙwayoyin cuta da danginsu.
Foregene kuma ya ƙaddamar da babban kayan aikin tantancewa don ƙwayoyin halittar da aka yi niyya, wanda yake da sauri kuma yana iya yin jujjuya rubutu da halayen qPCR ba tare da cirewar RNA ba.
Haɗin Samfura
Kit ɗin Wayar Kai tsaye RT-qPCR—Taqman/SYBR GREEN I
Don ƙarin bayanin samfur, tuntuɓi:
Lokacin aikawa: Satumba-02-2022
