Mumakore gumi apfuura, tekinoroji yekugadzira gene yakavakirwa paCRSPR yakagadzira nekukurumidza, uye yakashandiswa zvakabudirira mukurapa kwezvirwere zvemajini uye kenza mumiedzo yekiriniki yevanhu.Panguva imwecheteyo, masayendisiti kutenderera pasirese anogara achibaya maturusi matsva ane gene editing kugona kugadzirisa matambudziko eiyo iripo gene editing zvishandiso uye sarudzo.

MunaGunyana 2021, timu yaZhang Feng yakaburitsa bepa mujenari reScience [1], uye yakaona kuti akawanda ma transposter akadhindwa RNA akatungamira nucleic acid enzymes ndokuitumidza iyo Omega system (inosanganisira ISCB, ISRB, TNP8).Chidzidzo ichi zvakare chakawana kuti iyo Omega system inoshandisa chikamu cheRNA kutungamira yekucheka DNA mbiri mbiri ketani, iyo ωRNA.Zvinotonyanya kukosha, aya nucleic acid ma enzymes idiki kwazvo, angangoita makumi matatu muzana eCAS9, zvinoreva kuti anogona kunge ari mukana wekuendeswa kumaseru.

Musi waGumiguru 12, 2022, timu yaZhang Feng yakaburitswa mujenari reMasikirwo rine musoro unoti: Structure of the Omega Nickase ISRB in Complex with ωrna uye Target DNA [2].

Chidzidzo ichi chakaongororazve chando che electron microscope chimiro che ISRB-ωRNA uye chinangwa cheDNA yakaoma muOmega system.

ISCB ndiyo tateguru weCAS9, uye ISRB chinhu chimwe chete chekushaikwa kweHNH nucleic acid domain yeISCB, saka saizi idiki, ingangoita mazana matatu nemakumi mashanu amino acids.DNA inopawo hwaro hwekumwe kusimudzira uye shanduko yeinjiniya.

RNA-inotungamirwa IsrB inhengo yemhuri yeOMEGA yakavharidzirwa neIS200/IS605 superfamily of transposons.Kubva pakuongorora phylogenetic uye kugovera nzvimbo dzakasiyana, IsrB inogona kunge iri yekutanga yeIscB, inova tateguru weCas9.

Muna Chivabvu 2022, Cornell University's Lovely Dragon Laboratory yakaburitsa bepa mujenari Sainzi [3], ichiongorora chimiro cheIscB-ωRNA uye maitiro ayo ekucheka DNA.

Kuenzaniswa neIscB neCas9, IsrB inoshaya HNH nuclease domain, REC lobe, uye mazhinji ePAM sequence-interacting domains, saka IsrB idiki zvakanyanya pane Cas9 (chete nezve 350 amino acids).Nekudaro, iyo diki saizi yeIsrB yakaenzana neyakakura gwara RNA (yayo omega RNA inenge 300 nt kureba).

Chikwata chaZhang Feng chakaongorora iyo cryo-electron maikorosikopu chimiro cheIsrB (DtIsrB) kubva munyoro-inopisa anaerobic bhakitiriya Desulfovirgula thermocuniculi uye yakaoma yaro yeωRNA uye DNA yakanangana.Ongororo yemaitiro yakaratidza kuti iyo yakazara chimiro cheIsrB protein yakagovanisa musana wechimiro neCas9 protein.

Asi mutsauko ndewekuti Cas9 inoshandisa iyo REC lobe kufambisa kucherechedzwa kwechinangwa, nepo IsrB ichitsamira pane yayo ωRNA, chikamu cheiyo inoumba yakaoma-matatu-dimensional chimiro chinoita seREC.

Kuti unzwisise zvirinani shanduko yeIsrB neCas9 panguva yekushanduka kubva kuRuvC, timu yaZhang Feng yakaenzanisa yakanangwa DNA-inosunga zvimiro zveRuvC (TtRuvC), IsrB, CjCas9 uye SpCas9 kubva kuThermus thermophilus.

Ongororo yezvimiro yeIsrB uye ωRNA yayo inojekesa kuti IsrB-ωRNA inoziva sei pamwe nekutsemura DNA yakanangana, uye inopawo hwaro hwekuwedzera budiriro uye engineering yeiyi miniaturized nuclease.Kuenzanisa nemamwe masisitimu anotungamirwa neRNA anoratidza kudyidzana kunoshanda pakati pemapuroteni neRNAs, kusimudzira manzwisisiro edu eiyo biology uye shanduko yeaya akasiyana masisitimu.

Links:

1.https://www.science.org/doi/10.1126/science.abj6856

2.https://www.science.org/doi/10.1126/science.abq7220

3.https://www.nature.com/articles/s41586-022-05324-6