GENETIC CONSTRUCTS ENCODING NUCLEASES Cas9-BE4-Gam AND Cas9-ABE 7.10, WHICH ARE DIRECTED INTO MITOCHONDRIA OF HUMAN CELLS Russian patent published in 2019 - IPC C12N15/63 A61K48/00 C12N15/55 C12N15/53 C12N15/62 

FIELD: medicine.

SUBSTANCE: invention refers to medicine, hereditary disease therapy and molecular biology and can be used to edit point pathogenic mutations associated with hereditary mitochondrial pathologies. Genetic constructs pMitoCas9-BE4-Gam and pMitoCas9-ABE7.10, encoding Cas9-BE4-Gam and Cas9-ABE7.10 nucleases, respectively, are imported into mitochondria, where the point mutations in mtDNA are corrected by recognizing a specific region of the sequence by interacting with a specific RNA guide and subsequent deamination of the nucleotide base. Further, during replication of the mtDNA molecule, a nucleotide complementary to the nucleotide is used opposite the deaminated base, which is a "corrected version" of the mutation. Thus, Cas9-BE4-Gam nuclease allows correcting the mutation C:G by T:A, whereas Cas9-ABE7.10 allows correcting more specific substitutions A:T for G:C. System selection is determined by the type of point mutations requiring editing.

EFFECT: invention provides a system for editing point mutations in mtDNA and a method for delivering nucleases into mitochondria.

2 cl, 4 dwg