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US 12,188,037 B2Granted
Synthetic combinatorial AAV3 capsid library
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsSergei Zolotukhin, Damien Marsic
Life of this patent
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Abstract
Compositions and methods for producing modified AAV Cap genes and combinatorial libraries of chimeric AAV vectors and virions in an AAV serotype 3 background. Selecting for modified AAV3 virions displaying cell- or tissue-specific tropisms differing from WT AAV3. Using the synthetic combinatorial AAV3 capsid libraries for introducing into a selected target host cells one or more nucleic acid molecules useful in diagnostic and/or therapeutic gene-therapy regimens.
Claims4
A non-naturally occurring nucleic acid molecule comprising:
- (a) a first nucleic acid sequence encoding at least one AAV Rep protein from serotype 3;
- and
- (b) a second nucleic acid sequence encoding an AAV3B VP1 Cap protein;
- wherein the AAV3B VP1 Cap protein comprises a variant variable region VII (VR-VII) comprising a plurality of amino acid substitutions relative to the wildtype AAV3B VP1 Cap protein VR-VII sequence set forth in amino acids 306-317 of SEQ ID NO:
- 4, wherein the variant VR-VII comprises:
- a first amino acid that corresponds to amino acid 306 of SEQ ID NO:
- 4 and is E;
- a second amino acid that corresponds to amino acid 307 of SEQ ID NO:
- 4 and is independently selected from the group consisting of N, S and D;
- a third amino acid that corresponds to amino acid 308 of SEQ ID NO:
- 4 and is independently selected from the group consisting of S, G and A;
- a fourth amino acid that corresponds to amino acid 309 of SEQ ID NO:
- 4 and is independently selected from the group consisting of T, K, N, R, S, E, D and A;
- a fifth amino acid that corresponds to amino acid 310 of SEQ ID NO:
- 4 and is independently selected from the group consisting of K, T, R, E and G;
- a sixth amino acid that corresponds to amino acid 311 of SEQ ID NO:
- 4 and is independently selected from the group consisting of N, T, D, A and G;
- a seventh amino acid that corresponds to amino acid 312 of SEQ ID NO:
- 4 and is D;
- an eighth amino acid that corresponds to amino acid 313 of SEQ ID NO:
- 4 and is independently selected from the group consisting of A, T and I;
- a ninth amino acid that corresponds to amino acid 314 of SEQ ID NO:
- 4 and is independently selected from the group consisting of E and A;
- a tenth amino acid that corresponds to amino acid 315 of SEQ ID NO:
- 4 and is independently selected from the group consisting of N, I, D, V, Y and F;
- an eleventh amino acid that corresponds to amino acid 316 of SEQ ID NO:
- 4 and is independently selected from the group consisting of E and G;
- and
- a twelfth amino acid that corresponds to amino acid 317 of SEQ ID NO:
- 4 and is independently selected from the group consisting of K, R, S, Q, H, E, D and G.
27 more elements
Dependencies are inferred from the claim text.