Recombinant adeno-associated virus (rAAV) encoding GJB2 and uses thereof

• Main Authors: GREENBERG MICHAEL E, PETERS CHARLES WILLIAM DAVID, HERVATIN, STEPHEN, NAGY, MARK, A, CORY DANIEL P, IVANCHENKO MIKHAIL VLADIMIROVICH, GRIFFITHS, ERIC, C, BOOTH KEVIN T
• Format: Patent
• Language: Chinese; English
• Published: 03.11.2023
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

The present disclosure relates, at least in part, to compositions (e.g., isolated nucleic acids and rAAVs) and methods for the treatment of non-syndromic hearing loss and deafness (DFNB1) by delivering gap-linked beta2 (GJB2) protein to inner ear cells (e.g., fibroblasts and supportive cells of Ketti and nearby regions) that normally express GJB2. The isolated nucleic acids of the present disclosure comprise an expression cassette wherein the expression cassette comprises a gap-linked beta2 (GJB2) gene regulatory element (GRE) (e.g., a GJB2 enhancer, a GJB2 promoter, GJB2 5 'UTR and/or GJB2 3' UTR) and a nucleotide sequence encoding a GJB2 protein. 本公开至少部分涉及通过递送间隙连接β2(GJB2)蛋白至正常情况下表达GJB2的内耳细胞(例如，成纤维细胞和柯蒂氏器的支持细胞和附近区域)治疗非综合症性听力缺失和耳聋(DFNB1)的组合物(例如，分离的核酸和rAAV)和方法。本公开的分离的核酸包含表达盒，其中该表达盒包含间隙连接β2(GJB2)基因调控元件(GRE)(例如，GJB2增强子、GJB2启动子、GJB2 5'UTR和/或GJB2 3'UTR)和编码GJB2蛋白的核苷酸序列。