TARGETABLE RAAV VECTORS FOR GENE THERAPY AGAINST HIV

描述：（改编自申请人的摘要） 目的是开发基因治疗载体， 用于治疗HIV感染的核酶。 虽然取得了巨大的成功 已经在开发具有抗病毒作用的核酶方面取得了进展， 与小分子药物相当的活性，基因递送到初级 细胞一直是一个基本问题。 为了克服这个问题 障碍，这些研究人员已经开始开发细胞类型特异性 CD 4和CD 34细胞表面蛋白的靶向载体。 这 该技术是基于将“靶向部分”掺入到 腺相关病毒载体（AAV）帽蛋白作为融合分子。 到目前为止，单链融合已经取得了一定的成功， 抗体可变区（ScF）与AAV Vp 2蛋白的N-末端。 他们的短期目标是优化转导 这些载体的功效。 为了实现这一目标，他们将 以下问题：1）改变衣壳蛋白或 融合末端能提高转导效率？ 2)并 将靶向分子的大小从250个氨基酸的ScF 20个氨基酸的合成结合肽改善转导 效率？ 3)消除AAV与其正常细胞结合的突变 受体被掺入具有单嗜性的可靶向载体中 感兴趣的细胞的转导？ 拟议商业应用：不可用

DESCRIPTION: (Adapted from Applicant's Abstract) The long-term objective is to develop gene therapy vectors that deliver hair-pin ribozymes for the treatment of HIV infection. Although great success has been achieved in the development of ribozymes that have antiviral activities comparable to small molecule drugs, gene delivery to primary cells has been a fundamental problem. In an effort to overcome this obstacle, these investigators have begun to develop cell-type specific targetable vectors for CD4 and CD34 cell surface proteins. This technology is based on incorporation of "targeting moieties" into the adeno-associated virus vector (AAV) cap proteins as fusion molecules. Thus far, some success has been achieved by fusion of a single-chain antibody variable region (ScF) with the N-terminus of AAV Vp2 protein. Their short-term goal in this proposal is to optimize the transduction efficiency of these vectors. To achieve this goal, they will address the following questions: 1) Does changing the capsid protein or terminus for fusion give improved transduction efficiency? 2) Does decreasing the size of the targeting molecule from a 250 amino acid ScF to a 20 amino acid synthetic binding peptide improve transduction efficiency? 3) Can mutations which eliminate AAV binding to its normal receptor be incorporated into the targetable vectors with mono-tropic transduction of cells of interest? PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE