TY - JOUR
T1 - Site-specific modification of adeno-associated viruses via a genetically engineered aldehyde tag
AU - Liu, Yarong
AU - Fang, Yun
AU - Zhou, Yu
AU - Zandi, Ebrahim
AU - Lee, Chi Lin
AU - Joo, Kye Il
AU - Wang, Pin
PY - 2013/2/11
Y1 - 2013/2/11
N2 - 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.
AB - 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.
KW - adeno-associated virus
KW - aldehyde tags
KW - antibody conjugation
KW - bioorthogonal chemistry
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=84873366065&partnerID=8YFLogxK
U2 - 10.1002/smll.201201661
DO - 10.1002/smll.201201661
M3 - Article
C2 - 23038676
AN - SCOPUS:84873366065
SN - 1613-6810
VL - 9
SP - 421
EP - 429
JO - Small
JF - Small
IS - 3
ER -