Computationally designed adeno-associated virus (AAV) Rep 78 is efficiently maintained within an adenovirus vector.

ABSTRACT: Adeno-associated virus (AAV) is a single-stranded parvovirus retaining the unique capacity for site-specific integration into a transcriptionally silent region of the human genome, a characteristic requiring the functional properties of the Rep 78/68 polypeptide in conjunction with AAV terminal repeat integrating elements. Previous strategies designed to assemble these genetic elements into adenoviral (Ad) backbones have been limited by the general intolerability of AAV Rep sequences, prompting us to computationally reengineer the Rep gene by using synonymous codon pair recoding. Rep mutants generated by using de novo genome synthesis maintained the polypeptide sequence and endonuclease properties of Rep 78, while dramatically enhancing Ad replication and viral titer yields, characteristic

SUBMITTER: Sitaraman V 

PROVIDER: S-EPMC3161519 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature