Metabolically activated recombinant viral vectors and methods for their preparation and use
DCFirst Claim
1. A recombinant adeno-associated virus (rAAV) preparation, which rAAV virus preparation is essentially free of helper virus, comprising an rAAV particle, wherein the rAAV particle comprises an rAAV genome, wherein the rAAV genome comprises a heterologous nucleotide sequence comprising a coding region and one or more inverted terminal repeat (ITR) sequences flanking said heterologous sequence, wherein the total amount of unique sequence present in the heterologous sequence is about one-half of the heterologous sequence and wherein the heterologous sequence forms intrastrand base pairs along most or all of its length such that expression of the coding region is enhanced relative to an rAAV vector that lacks sufficient intrastrand base pairing to enhance expression.
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Abstract
Recombinant viral vectors, especially parvovirus vectors such as adeno-associated virus (AAV) vectors, capable of enhanced expression of heterologous sequences, and methods for their construction and use, are provided. The vectors have a structure, or are capable of rapidly adopting a structure, which involves intrastrand base pairing of at least one region in a heterologous sequence.
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Citations
6 Claims
- 1. A recombinant adeno-associated virus (rAAV) preparation, which rAAV virus preparation is essentially free of helper virus, comprising an rAAV particle, wherein the rAAV particle comprises an rAAV genome, wherein the rAAV genome comprises a heterologous nucleotide sequence comprising a coding region and one or more inverted terminal repeat (ITR) sequences flanking said heterologous sequence, wherein the total amount of unique sequence present in the heterologous sequence is about one-half of the heterologous sequence and wherein the heterologous sequence forms intrastrand base pairs along most or all of its length such that expression of the coding region is enhanced relative to an rAAV vector that lacks sufficient intrastrand base pairing to enhance expression.
Specification