Genomic Safe Harbors: Yadda Za'a Yi Amfani da Su Don Amintaccen Maganin Halittu

Genomic safe harbors (GSH) yankuna ne na kwayoyin halittar dan adam da aka gano kuma aka sanya su a matsayin amintattun wuraren sauka don sabbin kwayoyin halittar warkewa. Waɗannan wuraren ba su da sauran abubuwan halitta waɗanda za su iya haifar da matsala idan za su yi hulɗa tare da sabuwar kwayar halitta. Ta hanyar amfani da GSHs, masana kimiyya za su iya tabbatar da cewa duk wani canje-canje da aka yi ga kwayar halittar kwayar halitta za a iyakance shi zuwa wurin da ake so kuma ba zai haifar da wani sakamako mara niyya ba.

A yau Jami'ar Harvard shared a rahoto akan Phys.org don sanar da cewa rukuni na mutanen da ke nazarin kwayoyin halitta a Harvard's Wyss Institute da ETH Zurich a Switzerland sun sami wurare masu aminci a cikin kwayoyin halitta. Wannan shi ne don sanya sababbin kwayoyin halitta a ciki ba tare da canza wasu sassan kwayoyin halitta wanda zai iya zama mummunan ga marasa lafiya ba.

Menene tashar jiragen ruwa masu aminci na genomic (GSHs)?

GSHs na iya yuwu a yi amfani da su don ɗaukar sabbin hanyoyin jiyya a cikin aminci. Alal misali, idan majiyyaci yana fama da cututtukan ƙwayoyin cuta, masana kimiyya za su iya amfani da GSHs don shigar da lafiyayyen kwafin kwayoyin halitta a cikin kwayoyin halittar majiyyaci. Wannan zai ba marasa lafiya damar samar da madaidaicin furotin da ake buƙata don magance cutar su. Hakanan ana iya amfani da GSHs don gyara maye gurbi waɗanda ke da alhakin haifar da cutar kansa.

Yayin da GSHs ke ba da hanya mai ban sha'awa don isar da sabbin hanyoyin warkewar kwayoyin halitta cikin aminci, ana buƙatar ƙarin bincike don tantance mafi kyawun hanyar amfani da su. Masana kimiyya har yanzu suna buƙatar gano wuraren da kwayoyin halitta suke da aminci don gyarawa da kuma yadda mafi kyawun saka sabbin kwayoyin halitta a cikin sel. Hakanan akwai haɗarin cewa za a iya amfani da GSHs don ƙirƙirar 'jarirai masu tsarawa' ta hanyar canza kwayoyin halitta ta hanyar da za ta iya inganta ko canza takamaiman halaye. Saboda wannan dalili, yana da mahimmanci don tabbatar da cewa duk wani canje-canjen da aka yi ga kwayoyin halitta ta amfani da GSHs suna da aminci kuma ana iya juyawa.

Ƙungiyar masana kimiyya a Harvard's Wyss Institute for Biologically Inspired Engineering, Harvard Medical School (HMS), da ETH Zurich a Switzerland sun ƙirƙiri wata sabuwar hanya don tantance wuraren saukowa tare da babbar dama don samun nasara don amintaccen shigar da kwayoyin halitta na warkewa da su. magana mai ɗorewa a cikin nau'ikan tantanin halitta da yawa. Biyu daga cikin shafukan GSH 2,000 za a iya tabbatar da su tare da hanyoyin kwantar da tarzoma na T cell, alal misali, da kuma magungunan Vivo don cututtukan da zasu iya shafar fatar mutane. Ta hanyar zayyana wuraren GSH don sadar da kwayar halitta mai ba da rahoto a cikin ƙwayoyin T, da kuma kwayar warkewa a cikin ƙwayoyin fata, sun nuna amintaccen magana mai dorewa na sabbin ƙwayoyin halittar da aka gabatar. 

Har ila yau mai ban sha'awa: David R. Liu - Shin Za Mu iya Magance Cututtukan Halitta ta hanyar Sake rubuta DNA? 

Masu bincike sun kirkiro wata hanya ta gano wurare masu aminci a cikin kwayoyin halittar dan adam inda za a iya shigar da sabbin kwayoyin halitta ba tare da haifar da wasu canje-canjen da ba a yi niyya ba. Sun yi haka ne ta hanyar nazarin wurare 2000 daban-daban a cikin kwayoyin halitta sannan suka gwada biyu daga cikinsu. Sun nuna cewa sabbin kwayoyin halitta za a iya bayyana su cikin aminci a cikin sel masu amfani da waɗannan rukunin yanar gizon. Mataki na gaba shine yin amfani da wannan bayanin don ƙirƙirar amintattun hanyoyin magance cututtuka kamar ciwon daji. Wannan muhimmin mataki ne na ci gaba a fannin maganin kwayoyin halitta kuma zai taimaka mana mu guji duk wani lahani mai cutarwa. Tashar jiragen ruwa masu aminci na genomic suna ba da hanyar shigar da sabbin kwayoyin halitta a cikin kwayoyin halitta lafiya, kuma ana iya amfani da wannan fasaha nan gaba don magance cututtuka daban-daban.

Hankali daga cikin ƙungiyar bincike

Manyan mutane a cikin wannan bincike sun bayyana ra'ayoyinsu game da rahoton. “Yayin da za a iya amfani da GSHs azaman dandamali na saukar da duniya don yin niyya ga kwayoyin halitta, kuma ta haka ne ke haɓaka haɓakar ilimin halittar jini da hanyoyin kwantar da hankali, ya zuwa yanzu babu wani wuri na kwayar halittar ɗan adam da ya tabbatar da cikakkiyar ingancinsa. Dukkansu an yarda da su ne kawai don aikace-aikacen bincike, ”in ji Wyss Core Faculty memba George Church, Ph.D., babban marubuci kan binciken. "Wannan ya sa tsarin haɗin gwiwar da muka ɗauka don ingantattun GSHs wani muhimmin ci gaba. Tare da ƙarin ingantattun kayan aikin haɗa kwayoyin halitta waɗanda muke haɓakawa a cikin dakin gwaje-gwaje, waɗannan GSHs na iya ƙarfafa yunƙurin fassarar asibiti iri-iri na gaba."

"A cikin wannan mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki-mataki yankunan da ke sanya sunadaran sunadaran, gami da sunadaran da suka shiga cikin samuwar ciwace-ciwacen daji, da kuma yankuna da ke sanya wasu nau'ikan RNA tare da ayyuka a cikin maganganun kwayoyin halitta da sauran su. salula matakai. Mun kuma kawar da yankunan da ke dauke da abin da ake kira abubuwan haɓakawa, waɗanda ke kunna bayyanar kwayoyin halitta, sau da yawa daga nesa, da kuma yankunan da ke kunshe da cibiyoyi da ƙarshen chromosomes don kauce wa kuskure a cikin maimaitawa da rarraba chromosomes a lokacin rarrabawar kwayar halitta, "in ji farko. - marubuci Erik Aznauryan, Ph.D. "Wannan ya bar mu da kusan 'yan takara 2,000 da za a ci gaba da bincike don dalilai na asibiti da ilimin halittu."

Tawagar ta kalli rukunin GSH guda biyu a cikin sel ɗan adam waɗanda ke da sha'awa ta musamman don maganin tantanin halitta da kwayoyin halitta. Sun bincika waɗannan rukunin yanar gizon a cikin ƙwayoyin rigakafi na T da ƙwayoyin fata, bi da bi. Ana amfani da ƙwayoyin T a yawancin hanyoyin kwantar da ƙwayoyin salula don magance ciwon daji da cututtuka na autoimmune. Waɗannan hanyoyin kwantar da hankali za su iya zama mafi aminci idan an shigar da kwayar halittar mai karɓa a cikin GSH. Har ila yau, cututtukan fata da ke haifar da maye gurbi masu cutarwa a cikin kwayoyin halitta masu sarrafa aikin sel a cikin nau'ikan fata daban-daban na iya yiwuwa a warke su ta hanyar sakawa da kuma bayanin dogon lokaci na ingantaccen kwafin halittar da aka canza zuwa GSH na rarraba ƙwayoyin fata.

Wurin GSH da aka bincika a cikin kwayar halittar kwayar halitta T yana cikin yankin da aka sani da "tashar jiragen ruwa mai aminci" don mutagenesis na shigar. Wannan kalmar tana nufin ƙananan haɗarin haifar da ciwon daji ko wasu canje-canje masu cutarwa a cikin sel lokacin da aka shigar da sababbin kwayoyin halitta a cikin wannan rukunin yanar gizon. Tawagar ta gano cewa, ko da lokacin da aka shigar da kwayar halittar mai karɓa a cikin wannan tashar jiragen ruwa mai aminci, har yanzu akwai ƙarancin haɗarin haifar da canje-canjen da ba a yi niyya ba a cikin kwayoyin halitta. Wannan yana nuna cewa ana iya amfani da rukunin GSH don amintar da sabbin ƙwayoyin jiyya ba tare da haifar da haɗari ga marasa lafiya ba.

“Mun gabatar da kwayar halittar mai ba da labari mai kyalli cikin sabbin GSH guda biyu a cikin sel na T na farko da aka samu daga su jini. Bugu da kari, mun shigar da kwayar halittar LAMB3 mai cikakken aiki, wanda shine furotin na waje a cikin fata, cikin GSH guda daya a cikin fibroblasts na farko na mutum, kuma mun lura da aiki mai dorewa,” kamar yadda Denitsa Milanova, Ph.D. "Yayin da waɗannan GSHs suna da matsayi na musamman don inganta matakan da tsayin daka na maganganun kwayoyin halitta a cikin mahaifa da 'ya'ya mata don maganin warkewa, Ina matukar farin ciki game da haɓakar haɓakar 'samun-aiki' na salula wanda zai iya haɓaka aikin yau da kullum na sel da gabobin. Sa'an nan kuma batun aminci yana da mahimmanci. "

"Bincike mai yawa da muka yi a GSH-engineered na farko na jikin mutum T ya nuna a fili cewa shigar da shi yana da ƙananan yuwuwar haifar da haɓakar ƙwayar cuta, wanda ko da yaushe shine babban damuwa lokacin da ake canza kwayoyin halitta don amfani da magani," in ji Sai Reddy, Sashen Kimiyya da Injiniyan Halittu na ETH Zurich. “Gano rukunin rukunin GSH da yawa kuma yana goyan bayan yuwuwar gina ƙarin ci gaba na hanyoyin kwantar da hankali na salula waɗanda ke amfani da transgenes da yawa don tsara ingantaccen martanin salon salula. Wannan yana da mahimmanci musamman a cikin injiniyoyin T cell don rigakafin cutar kansa. ”

Haɗin kai don ƙarawa juna, ba don yin takara a kimiyya ba

Haɗin kai koyaushe ya kasance muhimmin abu ga abubuwa da yawa a tarihin kimiyya. "Wannan ƙoƙarin haɗin gwiwar haɗin gwiwa yana nuna ikon haɗa hanyoyin lissafin lissafi tare da injiniyan kwayoyin halitta yayin da ake mai da hankali kan fassarar asibiti. Gano GSHs a cikin kwayoyin halittar ɗan adam zai ƙara haɓaka ƙoƙarin ci gaba na gaba na gaba da aka mayar da hankali kan aikin injiniya mafi inganci kuma mafi aminci ga kwayoyin halitta da hanyoyin kwantar da hankali, "in ji Daraktan Kafa Wyss Donald Ingber, MD, Ph.D.

Ko da yake irin wannan binciken ba ya shahara a duk wurare, an sami ayoyi masu mahimmanci da yawa tun daga lokacin Human genome Project An fara shi ne a cikin 1990, da nufin gano jerin DNA na dukkanin kwayoyin halittar ɗan adam. An kammala aikin a shekara ta 2003, kuma yawancin binciken da aka samu shine ƙwarin gwiwa don fara ƙarin bincike kamar aikin a kusa da tashar jiragen ruwa masu aminci tare da manufar taimakawa wajen warkar da cututtuka. 

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Hoto Credit: Duk hotuna da aka nuna alama ne. The siffar hoto An yi ta Cultura Allies. The photo Viacheslav Lakobchuk a cikin jikin labarin ya dauki shi.
Sanarwa na Edita: An gajarta wasu sassan abubuwan da aka ambata kuma an tattara su don tsabta. Ba a canza bayanin da ke ciki ba.