Abhishek SamantaArun IyerMansoor AmijiRavi Sundaram
The idea of using small interfering RNA (siRNA) for therapeutic purposes has been tested in the last few years with the pioneering work of Elbashir, et al. RNA interference (RNAi) has emerged as a powerful tool for specific gene silencing in gene therapy. RNAi can be achieved by using small interfering RNA (siRNA) as tools for target gene silencing in tumor cells. siRNA inhibits protein expression of gene by specific sequence-dependent degradation of its target messenger RNA (mRNA). Following the discovery, the therapeutic potential of the siRNA was immediately realized. siRNA have emerged as potential drug candidates that can, when delivered properly, harness the specific gene in a consistent and predictable manner. siRNA can be chemically modified and scaled-up produced. The initial in vivo therapeutic effiects of siRNA were established using free siRNAs for various diseases although free siRNAs are not ideal to produce efficient and predictable therapeutic effects. While siRNA has been shown to be effective for short-term gene inhibition in mammalian cell lines, its use for stable transcriptional knockdown have been problematic. siRNA nucleic acids have inherent stability and delivery problems for clinical applications. They have poor cellular membrane permeability and limited stability in vivo. The main obstacle to RNAi therapy is in delivering oligonucleotides to the cytoplasm where it can guide sequence-specific mRNA degradation. In addition, the human body is well-equipped to destroy double-stranded RNA circulating in blood and prevent it from entering cells. Moreover, the efficiency of siRNA passively entering target cells is usually very low. To overcome these difficulties, there is a need to develop efficient siRNA delivery systems. Recently, different types of nano-particles have emerged as alternatives to plasmid or viral vectors for the delivery of siRNAs. Nanoparticles need to encapsulate siRNAs and protect them clearance and degradation. Ideally they need to be functionalized with targeting ligands, which may potentially improve the delivery specificity and efficiency.
Designing an algorithm to maximize drug loading in nano-polymers