CONJUGATE-BASED TARGETING OF ADENO-ASSOCIATED VIRUS VECTORS

Targeting of viral vectors to specific cell types not only offers an attractive method to achieve restricted expression of transgenes but also has the potential to achieve optimal results with a minimal vector dose, which is highly desirable in circumventing host immunity. Further, ablation of transduction to non-target cells may also minimize vector-associated toxicity. Recombinant adeno-associated virus vector (rAAV) is presently gaining attention as a powerful gene transfer vehicle due to the absence of any pathogenicity and a comparatively low vector-associated immunity. Despite these excellent safety profiles, a wider application of rAAV vectors is limited due to precincts in transduction efficiency of cell types. Although AAV vectors transduce cells of muscle and neuronal origin with increased efficiency, several other cell types are also infected with varying efficiency. Thus, development of targeted-AAV vectors with specific host affinity will largely benefit their application in gene therapy by both eliminating transduction of non-target cells and enhancing the transduction of otherwise refractory cells such as cells of hematopoietic origin. Most of the attempts to retarget AAV vectors have so far been carried out by genetic modification of the capsid structure. Limitations to such a modification include the size of AAV capsid for the inclusion of targeting ligands and absence of crystallographic structure of AAV capsid. In this situation, development of non-genetic approaches to retarget AAV through alternate cellular receptor could overcome some of these deficiencies. The present chapter will address these issues and discuss the possible ways of AAV retargeting by conjugate-based approaches.