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US 8,632,764 B2Granted
Directed evolution and in vivo panning of virus vectors
AssigneeThe University of North Carolina at Chapel Hill
InventorsXiao Xiao, Lin Yang
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Abstract
The present invention provides methods of achieving directed evolution of viruses by in vivo screening or “panning” to identify viruses comprising scrambled AAV capsids having characteristics of interest, e.g., tropism profile and/or neutralization profile (e.g., ability to evade neutralizing antibodies). The invention also provides scrambled AAV capsids and virus particles comprising the same.
Claims25
A nucleic acid encoding an AAV capsid, the nucleic acid comprising an AAV capsid coding sequence selected from the group consisting of:
- (a) the nucleotide sequence of FIG. 3A (M41) (SEQ ID NO:1);
- (b) a nucleotide sequence that is at least 98% identical to the nucleotide sequence of FIG. 3A (M41) (SEQ ID NO:1);
- (c) a nucleotide sequence that encodes the AAV capsid encoded by the nucleotide sequence of (a) but that differs from the nucleotide sequence of (a) due to the degeneracy of the genetic code;
- and
- (d) a nucleotide sequence that encodes an AAV capsid that is at least 98% identical to the AAV capsid encoded by the nucleotide sequence of (a) and that substantially retains at least one property of the AAV capsid encoded by the nucleotide sequence of (a).
2 more elements
Dependencies are inferred from the claim text.