MODIFIED CAPSID PROTEINS FOR IMPROVED DELIVERY OF PARVOVIRUS VECTORS Russian patent published in 2021 - IPC C07K14/15 A61P19/08 A61K35/76 

FIELD: biotechnology.

SUBSTANCE: invention relates to biotechnology. A parvovirus capsid protein is presented containing an amino acid sequence of a capsid protein derived from the serotype of an adeno-associated virus (AAV) or any other parvovirus with an icosahedral capsid structure T=1, while the variable region loop 1 (VR1) containing the amino acid residues 258-272 of the AAV1 capsid protein or the corresponding amino acid residues of another AAV or parvoviral capsid protein is modified by deleting and/or replacing one or more amino acid residues that will result in the destabilization of the loop region due to the targeted destruction of the hydrogen bond patterns created by these residues, and with the capsid protein containing such a modification giving the viral vector containing the capsid protein: a) increased transduction efficiency; and/or b) altered efficiency of tissue-specific transduction, resulting in increased transduction in one tissue compared to another tissue; compared to a viral vector involving a capsid protein that does not contain such a modification. The corresponding polynucleotide and parvovirus capsid are presented. A recombinant parvoviral vector for gene delivery is described, including: (a) the specified parvoviral capsid; and (b) a recombinant viral matrix containing: (i) a heterologous nucleic acid; and (ii) at least one inverted terminal repeat; with the recombinant viral matrix being encapsulated in the parvoviral capsid. In addition, a pharmaceutical composition containing the specified viral vector in a pharmacologically acceptable carrier is described. Methods of delivery of nucleic acid to the cell and to the individual using the specified viral vector or pharmaceutical composition are described. A method for producing a recombinant parvovirus particle is also presented.

EFFECT: invention makes it possible to increase the transduction and expands the arsenal of means for delivering nucleic acids to the cell or to the individual.

38 cl, 24 dwg, 11 tbl, 14 ex