The College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China.
Med Hypotheses. 2011 Feb;76(2):239-40. doi: 10.1016/j.mehy.2010.10.007. Epub 2010 Oct 30.
In recent years, a large number of researchers have paid much attention on small interfering RNA (siRNA) after the advent of RNA interference technology, which has been harnessed as an efficient way of sequence-specific gene silencing in gene therapy, enables elucidation of gene functions, and the identification of new drug targets. Despite tremendous progress has been made in novel delivery systems and vectors via formulation of polyplexes and conjugations, such as cationic polymers (LPEI, BPEI), cationic liposome (DOTAP), peptides (CPP), unmet needs still exist. Many cationic agents used for condensing siRNA often exhibits severe cytotoxicity, which limits clinical applications, and is obliged to be handled. Thus great interest in searching for novel and sophisticated polymeric vectors has been spurred. Herein we proposed a genetically synthetic protein-based polymer, which is also referred to as elastin-like polypeptides (ELPs) excerpted from human tropoelastin highly repetitive sequence, Val-Pro-Gly-Xaa-Gly, where the "guest residue" Xaa is any amino acid except Pro. Thus, if we alternate the "guest residue" Xaa to Lys or Arg, to a significant extent, it can emerge as a powerful cationic polymer for siRNA delivery carrier, and hopefully it will be put into practice in the near future.
近年来，随着 RNA 干扰技术的出现，大量研究人员对小干扰 RNA（siRNA）给予了高度关注，它已被用作基因治疗中序列特异性基因沉默的有效方法，能够阐明基因功能，并确定新的药物靶标。尽管在通过形成聚电解质和缀合（如阳离子聚合物（LPEI、BPEI）、阳离子脂质体（DOTAP）、肽（CPP））方面，新型递药系统和载体已经取得了巨大进展，但仍存在未满足的需求。许多用于缩合 siRNA 的阳离子试剂通常表现出严重的细胞毒性，这限制了其临床应用，并且必须进行处理。因此，人们对寻找新型复杂聚合物载体产生了浓厚的兴趣。在这里，我们提出了一种基于基因合成的蛋白质聚合物，也称为弹性蛋白样多肽（ELPs），它是从人胎球蛋白高度重复序列 Val-Pro-Gly-Xaa-Gly 中提取的，其中“客位残基”Xaa 是脯氨酸以外的任何氨基酸。因此，如果我们将“客位残基”Xaa 交替为赖氨酸或精氨酸，在很大程度上可以将其作为一种强大的阳离子聚合物用于 siRNA 递送载体，并且有望在不久的将来付诸实践。
