武汉云克隆科技股份有限公司

Abstract: Human therapeutics based on nucleic acid targeting rely on sequence-specific interactions between effector and target molecules to achieve beneficial effects through specific modification to the expression of targeted genes. A variety of such compounds are being tested in laboratories and in clinical trials to treat a range of genetic and acquired diseases. Efficient, safe and cost-effective delivery of nucleic acid–based drug candidates is required to enable therapeutic levels of targeted gene regulation and overall success of this exciting new class of therapeutics. For several types of compounds in this class, effective drug delivery relies on injection of formulated nucleic acids at the site of action or into the bloodstream. Oral delivery would excel as a treatment strategy as it could offer convenient and patient-friendly features, however, progress in this approach has been hampered by substantial challenges associated with biological barriers that limit oral activity of nucleic acid therapeutics (e.g., stability within and uptake of nucleic acids from the mammalian gastrointestinal tract, nucleases and membrane barriers). Considerable effort has been applied to improve the stability and uptake efficiency of orally administered nucleic acids by introducing chemical modifications and formulating with excipients; however, limited success has been reported thus far.

摘要：基于核酸目标的人类疗法依赖于效应物和靶标分子之间的序列特异性相互作用，通过对目标基因表达的特定修饰来达到有益的效果。在实验室和临床试验中，为了治疗一系列的遗传和后天疾病，大家都在测各种各样的化合物。核酸碱基候选药物的高效、安全且低成本的给药需要实现靶向基因调控的治疗水平和这一激动人心的新疗法的整体成功。对于这种分类中的几种化合物，有效的药物给药依赖于在功能区或血液中注入合成的核酸。口服给药将会成为一个优秀的治疗策略，因为它可以提供方便和便于患者使用的特性，然而，这种方法的进展受到生物屏碍的限制，该屏障会限制核酸治疗的口服活性（例如：哺乳动物胃肠道内部和摄入的核酸稳定性，核酸酶和膜屏障）。为了提高口服核酸的稳定性和吸收率，大量的工作用来引入化学修饰和制定辅料；然而，迄今为止，报告的成功案例十分有限。

使用试剂原文信息：In the present study, LDLRAP1 protein levels were evaluated in mouse liver using a commercial mouse LDLRAP1 ELISA kit (USCN Life Sciences; Wuhan, China).