Methods of treating ocular neovascular diseases using AAV2 variants encoding aflibercept

• Main Authors: GRISHANIN, LUSLAN, RILEY, BRIGITTE, HANNA KELLY, SCHAEFER-SWIER KELLY, TURPCU, ADAM, BECKMANN RICHARD
• Format: Patent
• Language: Chinese; English
• Published: 22.10.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

There is provided a method for treating an ocular neovascular disease in a subject comprising administering to the eye of the subject a unit dose of a recombinant adeno-associated virus (rAAV) particle wherein the rAAV particle comprises: a) a nucleic acid encoding a polypeptide and flanking an AAV2 inverted terminal repeat (ITR), the polypeptide comprises an amino acid sequence having at least about 95% identity to the amino acid sequence of SEQ ID NO: 35; and b) an AAV2 capsid protein comprising the amino acid sequence LGETTRP (SEQ ID NO: 14) inserted between positions 587 and 588 of the capsid protein wherein the amino acid residue number corresponds to the AAV2 VP1 capsid protein. 提供了用于治疗个体的眼部新生血管性疾病的方法，其包括向所述个体的眼睛施用单位剂量的重组腺相关病毒(rAAV)颗粒，其中所述rAAV颗粒包含：a)编码多肽且侧接AAV2反向末端重复序列(ITR)的核酸，所述多肽包含与SEQ ID NO:35的氨基酸序列具有至少约95％同一性的氨基酸序列；和b)AAV2衣壳蛋白，其包含插入在所述衣壳蛋白的位置587和588之间的氨基酸序列LGETTRP(SEQ ID NO:14)，其中所述氨基酸残基编号对应于AAV2VP1衣壳蛋白。