Department of Chemical Engineering, The Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-1462, USA.
Gene Ther. 2010 Nov;17(11):1384-9. doi: 10.1038/gt.2010.81. Epub 2010 May 27.
Adeno-associated viral (AAV) vectors, which are undergoing broad exploration in clinical trials, have significant promise for therapeutic gene delivery because of their safety and delivery efficiency. Gene delivery technologies capable of mediating localized gene expression may further enhance the potential of AAV in a variety of therapeutic applications by reducing spread outside a target region, which may thereby reduce off-target side effects. We have genetically engineered an AAV variant capable of binding to surfaces with high affinity through a hexa-histidine metal-binding interaction. This immobilized AAV vector system mediates high-efficiency delivery to cells that contact the surface and thus may have promise for localized gene delivery, which may aid numerous applications of AAV delivery to gene therapy.
腺相关病毒（AAV）载体在临床试验中得到了广泛的探索，由于其安全性和传递效率，它们在治疗性基因传递方面具有很大的应用前景。能够介导局部基因表达的基因传递技术可以通过减少目标区域以外的扩散，从而降低脱靶副作用，进一步增强 AAV 在各种治疗应用中的潜力。我们通过六组组氨酸金属结合相互作用，对能够与表面高亲和力结合的 AAV 变体进行了基因工程改造。这种固定化的 AAV 载体系统介导与表面接触的细胞高效传递，因此可能具有局部基因传递的潜力，这可能有助于 AAV 传递到基因治疗的众多应用。
