Site-specific modification of adeno-associated viruses via a genetically engineered aldehyde tag

Yarong Liu, Yun Fang, Yu Zhou, Ebrahim Zandi, Chi Lin Lee, Kye Il Joo, Pin Wang

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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. An aldehyde moiety can be genetically incorporated onto the capsid surface of adeno-associated viruses. This chemical handle can be selectively modified through bioorthogonal conjugation chemistry to functionally outfit virus coats with antibodies and peptides for targeted gene delivery, and labelling agents for imaging studies.

Original languageEnglish
Pages (from-to)421-429
Number of pages9
Issue number3
StatePublished - 11 Feb 2013


  • adeno-associated virus
  • aldehyde tags
  • antibody conjugation
  • bioorthogonal chemistry
  • targeted therapy


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