Small interfering RNA “siRNA”

RNA interference (RNAi) mechanisms have gained much popularity in the scientific community due to its potential to cause targeted knockdown of gene expression. RNAi is a natural defense mechanism for the invasion of exogenous genes. One year after the discovery of RNAi, “Small interfering RNA” or siRNA was discovered. This type of RNAi is a small sequence of RNA around 20–27 base pairs in length used to destroy target mRNA that is responsible for translation of a specific protein. They are a functional component of multiple RNA interfacing pathways within the cell. They can be endogenous, but most of the siRNA's functional components are produced through exogenous mechanisms. Micro RNAs or miRNA is often used synonymous with siRNA, although they differ in their target functionality. The cell can uptake dsRNA from its surroundings, it can be introduced through vectors or can be artificially injected into a cell of choice to control the action of a specific protein of interest. The key to recognition of the target mRNA is the antisense strand, which is the single most important determinant of effectiveness. The key proteins involved in the functionality of siRNA are Dicer, RNA induced silencing complex (RISC), and Argonaut (Argo2 in humans). This form of RNA interference has been explored to assess an assortment of cellular phenotypes including cytokinesis, apoptosis, insulin signaling, and cell differentiation. In recent years, many studies have shown therapeutic applications of siRNA knockdown functionality, but limitations of its delivery, stability, off target toxicity, and immunogenicity have remained significant concerns. With great reward comes risk, but currently there have been techniques used to decrease the aforementioned risks such as: chemical modifications to counteract destruction, decreased recognition by host immune system, and increase half-life of siRNA. More so, nanoparticles have been used to enhance the delivery, and receptor target delivery, which has helped direct this siRNA technology to a specific tissue type. Ultimately, there have been great advancements in siRNA technologies over the past two decades. The most recent milestones come in the form of three FDA approved therapeutic agents. FDA's first drug approval in 2018 was the drug Onpattro™ for polyneuropathy of hereditary transthyretin-mediated amyloidosis, GIvlaari™ in 2019, was approved for acute hepatic porphyria, and lastly as of November 2021, Oxlumo™ was approved for the treatment of primary hyperoxaluria type. Overall, implications of this technology in therapeutics appears to be extraordinarily promising.