Development of siRNA Nano-Carriers for In Vivo R&D and Gene Therapy

核酸是所有细胞过程的中心，染色体DNA作为遗传信息的存储装置，RNA分子直接控制基因表达，并通过基因表达控制每一种细胞功能。因此，临床应用短RNA分子（例如miRNA、siRNA）来“沉默”特定恶性基因的表达（称为RNA干扰的过程）可用于治疗遗传性和获得性疾病（例如癌症和病毒感染）的起源，而不仅仅是其症状。受其治疗潜力和临床前基因治疗和再生医学的杰出进展的刺激，RNA干扰（RNAi）在研发和制药中的应用是生物医学市场的一个快速增长的领域。然而，有一个主要的技术障碍：核酸通过细胞膜的运输被它们的大小和负电荷所阻碍。为了促进siRNA的细胞内递送，DELIVERICS开发了一种基于可生物降解纳米载体的突破性技术，该技术能够以非常高的效率无毒性地执行这一具有挑战性的任务;该技术目前作为用于“体外”研究的研发试剂盒商业化：SAFEctin转染试剂和SAFEctin-STEM。为了开发一种能够通过局部给药治疗皮肤病变的基因治疗药物，DELIVERICS（与爱丁堡大学合作）旨在优化其siRNA递送到皮肤细胞中的平台技术。这种可生物降解的载体，即所谓的LIFEctin载体，将解决研发和制药领域存在的商业机会，其中需要具有临床级安全性和可靠性的siRNA递送工具用于“体内”研发研究和开发有效的基于RNAi的药物。

Nucleic acids are at the very center of all cellular processes, with chromosomal DNA serving as a storage device for genetic information and RNA molecules directly controlling gene expression and, through this, each and every cellular function. Consequently, the clinical application of short RNA molecules (e.g. miRNA, siRNA) to “silence” the expression of specific malignant genes (process known as RNA interference) can be used to treat both genetic and acquired diseases (e.g. cancers and viral infections) at their origin, not merely their symptoms. Stimulated by its therapeutic potential and outstanding advances in preclinical gene therapy and regenerative medicine, the use of RNA interference (RNAi) in R&D and Pharma is a fast growing sector of the biomedical market. There is, however, a major technical hurdle: the transport of nucleic acids through cell membranes is blocked by their size and negative charge. To facilitate the intracellular delivery of siRNA, DELIVERICS developed a ground-breaking technology based on biodegradable nano-carriers able to carryout this challenging task at very high efficiency without toxicity; a technology currently commercialised as R&D kits for “in vitro” studies: SAFEctin Transfection Reagent and SAFEctin-STEM. Aiming to develop a gene therapy drug able to treat skin lesions by topical administration, DELIVERICS (in collaboration with the University of Edinburgh) aims to optimise its platform technology for siRNA delivery into skin cells. This biodegradable vehicle, so-called LIFEctin LOCAL, will address a commercial opportunity that exists in both the R&D and Pharma sectors, where siRNA delivery tools with clinical-grade safety and reliability are required for "in vivo" R&D studies and for developing efficient RNAi-based drugs.