Schmidt Michael, Voutetakis Antonis, Afione Sandra, Zheng Changyu, Mandikian Danielle, Chiorini John A
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Virol. 2008 Feb;82(3):1399-406. doi: 10.1128/JVI.02012-07. Epub 2007 Nov 28.
Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy. Recent isolations of novel AAV serotypes have led to significant advances by broadening the tropism and increasing the efficiency of gene transfer to the desired target cell. However, a major concern that remains is the strong preexisting immune responses to several vectors. In this paper, we describe the isolation and characterization of AAV12, an AAV serotype with unique biological and immunological properties. In contrast to those of all other reported AAVs, AAV12 cell attachment and transduction do not require cell surface sialic acids or heparan sulfate proteoglycans. Furthermore, rAAV12 is resistant to neutralization by circulating antibodies from human serum. The feasibility of rAAV12 as a vector was demonstrated in a mouse model in which muscle and salivary glands were transduced. These characteristics make rAAV12 an interesting candidate for gene transfer applications.
重组腺相关病毒(rAAV)是一种很有前景的基因治疗载体。最近新型AAV血清型的分离通过拓宽嗜性和提高基因转移至所需靶细胞的效率取得了重大进展。然而,仍然存在的一个主要问题是对几种载体存在强烈的预先存在的免疫反应。在本文中,我们描述了AAV12的分离和特性,AAV12是一种具有独特生物学和免疫学特性的AAV血清型。与所有其他报道的AAV不同,AAV12的细胞附着和转导不需要细胞表面唾液酸或硫酸乙酰肝素蛋白聚糖。此外,rAAV12对人血清中的循环抗体具有抗性。rAAV12作为载体在转导肌肉和唾液腺的小鼠模型中得到了证实。这些特性使rAAV12成为基因转移应用中一个有趣的候选者。