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TitleAtomic structure of a rationally engineered gene delivery vector, AAV2.5.
Journal, issue, pagesJ Struct Biol, Vol. 203, Issue 3, Page 236-241, Year 2018
Publish dateMay 18, 2018
AuthorsMatthew Burg / Claire Rosebrough / Lauren M Drouin / Antonette Bennett / Mario Mietzsch / Paul Chipman / Robert McKenna / Duncan Sousa / Mark Potter / Barry Byrne / R Jude Samulski / Mavis Agbandje-McKenna /
PubMed AbstractAAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 ...AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78 Å using cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2.5 residues exchanged from AAV2 to AAV1, Q263A, T265 (insertion), N706A, V709A, and T717N, were readily interpretable. Significantly, the surface loops containing these residues adopt the AAV1 conformation indicating the importance of amino acid residues in dictating VP structure.
External linksJ Struct Biol / PubMed:29775653 / PubMed Central
MethodsEM (single particle)
Resolution2.78 Å
Structure data

7452

6cbe

EMDB-7452, PDB-6cbe:
Atomic structure of a rationally engineered gene delivery vector, AAV2.5
Method: EM (single particle) / Resolution: 2.78 Å

Source
  • adeno-associated virus 2
KeywordsVIRUS / AAV / dependoparvovirus / gene therapy vector / retional design

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