Schwarzenberger P, Huang W, Oliver P, Osidipe T, Theodossiou C, Kolls J K
Department of Medicine, Louisiana State University Medical Center of New Orleans 70122, USA.
Am J Med Sci. 2001 Feb;321(2):129-36. doi: 10.1097/00000441-200102000-00004.
Targeted, specific receptor mediated gene transfer is a major goal of gene therapy research to accomplish gene transfer exclusively to the desired cell population.
First, the use of natural receptor for stem cell factor and transferrin receptor-targeted gene transfer using poly-L-lysine-based molecular conjugate vectors was evaluated in a panel of hematopoietic progenitor cell lines. Second, the ability of poly-L-lysine to enhance adenovirus mediated gene transfer efficiency was examined in different cell lines by using recombinant adenovirus-poly-L-lysine molecular conjugate conglomerates (recMCVEGFP).
Despite effective ligand internalization receptor, gene expression amplification in receptor positive cell lines was not uniformly observed. Therefore, using a poly-L-lysine-based, receptor-targeted vector, neither transferrin nor natural receptor for stem cell factor mediated gene transfer can be considered a universally applicable procedure that exclusively depends on the presence of receptors on the cell surface; rather, it is a cell specific phenomenon. In our model, poly-L-lysine is the major contributor for gene transfer to hematopoietic progenitor cells, mediating the initial vector-cell binding. Human progenitor cell lines are poorly transduceable with recombinant adenovirus vectors. This new poly-L-lysine-modified, adenovirus-based vector could overcome virus tropism restrictions and consistently achieve very high transduction efficiency (>90%) in cells otherwise refractory to adenovirus gene transfer.
Polylysine-based adenovirus vectors may have promise for situations in which high-efficiency gene transfer with transient high level transgene expression in hematopoietic cells is needed, such as leukemia vaccine protocols or for purging strategies in leukemia cell contaminated stem cell preparations.
靶向、特异性受体介导的基因转移是基因治疗研究的一个主要目标，旨在仅将基因转移至所需的细胞群体。
首先，在一组造血祖细胞系中评估了使用干细胞因子天然受体以及利用基于聚-L-赖氨酸的分子共轭载体进行转铁蛋白受体靶向基因转移的情况。其次，通过使用重组腺病毒-聚-L-赖氨酸分子共轭聚集体（recMCVEGFP）在不同细胞系中检测了聚-L-赖氨酸增强腺病毒介导的基因转移效率的能力。
尽管配体有效内化受体，但在受体阳性细胞系中并未一致观察到基因表达放大。因此，使用基于聚-L-赖氨酸的受体靶向载体，转铁蛋白或干细胞因子天然受体介导的基因转移都不能被视为仅依赖于细胞表面受体存在的普遍适用程序；相反，这是一种细胞特异性现象。在我们的模型中，聚-L-赖氨酸是基因转移至造血祖细胞中的主要促成因素，介导了初始的载体-细胞结合。人祖细胞系对重组腺病毒载体的转导能力较差。这种新型的聚-L-赖氨酸修饰的腺病毒载体可以克服病毒嗜性限制，并在原本对腺病毒基因转移有抗性的细胞中始终实现非常高的转导效率（>90%）。
基于聚赖氨酸的腺病毒载体对于需要在造血细胞中进行高效基因转移并伴有短暂高水平转基因表达的情况可能具有应用前景，例如白血病疫苗方案或用于清除白血病细胞污染的干细胞制剂中的清除策略。
