Knocking Down Barriers: Advances in siRNA Delivery

Abstract

RNA interference (RNAi) has been emerged as an effective method to silence a particular gene utilizing a sequence‐specific mechanism for gene regulation. It induces target mRNA degradation leading to a lower illness‐inducing gene product. RNAi represent a conserved mechanism. Novel concept of highly specific silencing of genes was revolutionized by the introduction of short interfering RNA (siRNA).This helped to overcome the drawbacks of RNAi and proved out to be a safer and efficient method than its counterpart finding its way into the pharmaceutical industry. Clinical trials enhanced the possibility of siRNA delivery and yielded promising results for the treatment of a wide range of illnesses but mainly for intractable diseases like cancer, inflammatory diseases, and genetic disorders. siRNA delivery methods were instrumental in developing it as a therapeutic, of which lipid encapsulation crept its way, to be a better in vivo delivery mechanism as it could be formulated effectively, being biodegradable, and has a lower toxicity level. However, the therapeutic potential of siRNA remains hampered due to a lack of a viable delivery method, a lower accuracy in tissue specificityand cytotoxicity. Hence the therapeutic usage of the method is in its budding stage. This review re‐examines the principle of siRNA, challenges in its delivery, and some recent advancesto overcome the obstacles in order to improve siRNA delivery.

DNA Nanostructures in Pharmaceutical Applications

“…Small interfering RNA(siRNA) is a type of double-stranded noncoding RNA that identifies and cleaves complementary mRNA. [25] The down-regulated mRNA induced to degrade protein expression. Different nanocarriers, similar to CpG, can be utilized to carry siRNA.…”

Iron Oxide Nanoparticles Decorated with Functional Peptides for a Targeted siRNA Delivery to Glioma Cells

“…23−25 Furthermore, siRNA is not known to exhibit genotoxic effects, as it interferes only with the translation of mRNA to knockdown the target gene. 26,27 Delivery of MGMT-targeting siRNA to glioma cells presents an avenue for safe and effective regulation of therapeutic resistance.…”

“…Recent advances in oncogenomics revealed new possibilities of identifying and regulating specific genes for cancer therapy. − Among these new opportunities, the delivery of short interfering RNA (siRNA) that can silence gene expression in a highly specific manner is a potent and highly effective approach to combat glioma by targeting genetic pathways that contribute to invasion, tumorigenesis, and therapy resistance. − As a promising and effective gene regulator, siRNA, a short double strand RNA with around 21 base pairs, suppresses the expression of target genes, which can allow elucidation of novel cellular and molecular mechanisms as well as inhibit disease-related genes. − The sequence of a therapeutic siRNA is specific to the mRNA sequence of the target gene, eliciting little to no off-site effects. − Furthermore, siRNA is not known to exhibit genotoxic effects, as it interferes only with the translation of mRNA to knockdown the target gene. , Delivery of MGMT-targeting siRNA to glioma cells presents an avenue for safe and effective regulation of therapeutic resistance.…”

Current Status of Natural Products/siRNA Co‐Delivery for Cancer Therapy

“…RNAi represent a conserved mechanism. Small interfering RNAs (siRNAs) has revolutionized the novel concept of highly specific silencing of genes [8] . The technology of small interfering RNAs (siRNAs) has already demonstrated tremendous potential as a novel type of diagnostic and therapeutic innovation for the intervention of various cancers [9] .…”

“…Small interfering RNAs (siRNAs) has revolutionized the novel concept of highly specific silencing of genes. [8] The technology of small interfering RNAs (siRNAs) has already demonstrated tremendous potential as a novel type of diagnostic and therapeutic innovation for the intervention of various cancers. [9] RNAi works on the basis that a double-stranded RNA (dsRNA) that is identical to the target sequence causes the deterioration of mRNA with specificity to its sequence.…”