Modified adeno-associated virus 1 (AAV1)

Modified AAV1 with VP3 capsid mutations at S507 and S587 addresses the challenge of imprecise AAV delivery by enhancing transduction efficiency and wound healing in corneal tissues for targeted gene therapy.

WO2025254596A1 Publication Date: 2025-12-11AGENCY FOR SCI TECH & RES +1
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Patent Information

Application Number
PCT/SG2025/050389
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-06-06
Filing Date
2025-06-06
Publication Date
2025-12-11

AI Technical Summary

Technical Problem

There is a need for efficient and specific delivery systems for gene therapeutics in corneal diseases, as existing adeno-associated virus (AAV) capsid delivery to specific ocular cell types is imprecise, limiting therapeutic development for corneal disorders and other organs.

Method used

A modified adeno-associated virus 1 (AAV1) with mutations at specific positions in the VP3 capsid protein, such as S507 and S587, enhances transduction efficiency and specificity for delivering therapeutic payloads like genes or CRISPR-Cas9 systems to corneal cells.

Benefits of technology

The modified AAV1 achieves up to 22-fold increased transduction efficiency and improved wound healing in corneal tissues, enabling effective gene delivery with lower vector doses.

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Abstract

The present disclosure provides a modified adeno-associated virus 1 (AAV1) comprising an AAV1 VP3 capsid protein, wherein the AAV1 VP3 capsid protein comprises one or more mutations at a position selected from the group consisting of: S507, and S587, relative to a wild-type AAV1 capsid protein sequence of SEQ ID NO: 65. The present disclosure also provides capsid proteins, nucleic acids, and compositions comprising said modified AAV1. The present disclosure also provides a method of treating a corneal disease to a subject, wherein the method comprises administering a therapeutically effective amount of the modified AAV1, or the composition of the disclosure to a subject, wherein the modified AAV1 comprises a payload for treating a corneal disease. Also provided by the present disclosure is a method of delivering a payload to a cornea of a subject, comprising administering the modified adeno-associated virus 1 (AAV1), or the composition of the disclosure, to the cornea of the subject.
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