Invention Grant
- Patent Title: Dual-AAV vector-based systems and methods for delivering oversized genes to mammalian cells
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Application No.: US16265864Application Date: 2019-02-01
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Publication No.: US11325956B2Publication Date: 2022-05-10
- Inventor: Sanford L. Boye , Shannon E. Boye , Frank Dyka , William W. Hauswirth
- Applicant: University of Florida Research Foundation, Incorporated
- Applicant Address: US FL Gainesville
- Assignee: University of Florida Research Foundation, Incorporated
- Current Assignee: University of Florida Research Foundation, Incorporated
- Current Assignee Address: US FL Gainesville
- Agency: Wolf, Greenfield & Sacks, P.C.
- Main IPC: C07K14/47
- IPC: C07K14/47 ; A61K48/00 ; C12N15/86

Abstract:
Disclosed are materials and methods for treating diseases of the mammalian eye, and in particular, Usher syndrome 1B (USH1B). The invention provides AAV-based, dual-vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. In one embodiment, vector systems are provided that include i) a first AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a suitable promoter followed by a partial coding sequence that encodes an N-terminal portion of a full-length polypeptide; and ii) a second AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a partial coding sequence that encodes a C-terminal portion of a full-length polypeptide, optionally followed by a polyadenylation (pA) signal sequence. In another embodiment, the vector system includes i) a first AAV vector polynucleotide comprising an inverted terminal repeat at each end, a suitable promoter followed by a partial coding sequence that encodes an N-terminal portion of a full-length polypeptide followed by a splice donor site and intron and ii) a second AAV vector polynucleotide comprising an inverted terminal repeat at each end, followed by an intron and a splice-acceptor site for the intron, followed by a partial coding sequence that encodes a C-terminal portion of a full-length polypeptide, optionally followed by a polyadenylation (pA) signal sequence. The coding sequence or the intron sequence in the first and second AAV vectors preferably includes a sequence region that overlaps.
Public/Granted literature
- US20190153050A1 DUAL-AAV VECTOR-BASED SYSTEMS AND METHODS FOR DELIVERING OVERSIZED GENES TO MAMMALIAN CELLS Public/Granted day:2019-05-23
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