Journal
SMALL
Volume 9, Issue 3, Pages 421-429Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201201661
Keywords
aldehyde tags; targeted therapy; adeno-associated virus; antibody conjugation; bioorthogonal chemistry
Categories
Funding
- National Institute of Health [R01AI68978, P01CA132681]
Ask authors/readers for more resources
As a consequence of their well-defined nanostructure and intrinsic bioactive functionality, virus-based nanoparticles have shown promise for mediating gene delivery. Adeno-associated virus (AAV) nanoparticles, which possess an excellent safety profile and therapeutic potential, hold potential for use in human gene therapy. However, because of their native tropisms, the applicability of AAV nanoparticles is often limited to restricted ranges of cells or tissues. Thus, retargeting AAV particles to the desired cell populations has continued to be a major research focus in many gene therapy applications. In this study, a general strategy is reported for nanoparticle targeting. This involves the site-specific modification of AAV type 2 (AAV2) by genetically incorporating a short peptide, in this case an aldehyde tag, in the viral capsid. Such a tag can be exploited for site-specific attachment of targeting molecules and allows for further introduction of targeting antibodies or ligands. It is shown that this modification neither affects the level of infectious viral titer nor intracellular trafficking properties. Furthermore, the site-specific conjugation of targeting antibodies could significantly enhance viral transduction to those target cells that have otherwise exhibited very low permissiveness to AAV2 infection. This method also allows the functional incorporation of RGD peptides onto AAV2 for enhanced delivery with implications for cancer gene therapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available