Ристоглоген аутогемцел

Prop. INN (наименование, предложенное ВОЗ)

autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) obtained from peripheral blood by leukapheresis, genetically modified ex vivo by electroporation of a guide RNA (gRNA) that targets the two γ-globin gene (HBG1 and HBG2) promotors and a messenger RNA (mRNA) that encodes the adenine base editor 8.8 (ABE8.8). When introduced into CD34+ cells by electroporation the gRNA binds to the translated ABE8.8 protein, which targets the promoter regions of HBG1 and HBG2, resulting in adenine to inosine modifications which subsequently leads to an A to G change.
The ABE8.8 mRNA is composed of three parts: (i) an impaired form of the Streptococcus pyogenes CRISPR-associated nuclease Cas9, referred to as Cas9 D10A nickase (nCas9- D10A), (ii) an Escherichia coli derived TadA deaminase that catalyses the adenosine to inosine conversion within a small activity window along the exposed, single-stranded DNA (ssDNA) formed within the R-loop, (iii) a C-terminal nuclear localization signal (NLS).
The cell suspension is enriched for CD34+ cells using magnetic bead separation. Following electroporation, the cells are cultured in media containing thrombopoietin, Fms-related tyrosine kinase 3 ligand (Flt3L), and stem cell factor (SCF). The substance consists of cells with ≥85% CD45+ and ≥75% CD34+ purity and ≥75% on-target editing.

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