RNA interference has been one of molecular biology’s most groundbreaking work in recent times. After having won the Nobel Prize in 2006, studies on RNA interference in gene silencing have only become more extensive. But, it is yet to be translated into its own class of medicine. RNAi therapeutics has the potential to become the treatment method for a large variety of medical conditions from cancers to Parkinson’s disease to viral pandemic outbreaks. However, their evolutionary defenses still allow invading RNA to get inside cells. It’s no wonder that much of the research goes into trying to develop an RNAi delivery system.

What is RNA interference?

Every cell in the human body has a nucleus, which contains DNA. It is the DNA’s job to instruct cells to create protein, required for every bodily function. These instructions, sent through a messenger-RNA or mRNA, could sometimes be incorrect, and trigger a problem, which shows up as symptom and is diagnosed as a disease. RNA interference begins with identifying a siRNA that matches with the mRNA and introducing a double-strand siRNA into the cell. Once it’s inside the cell, it splits and the complementary strand is sent to a protein complex: RNA-inducing silencing complex (RISC). RISC finds the matching rogue mRNA and cleaves it, disabling its use as a protein.

GAlNAc-siRNA treatment for liver conditions

GAlNAc has the ability to treat many liver conditions such as NASH and liver fibrosis. All it needs is an efficient delivery platform. Through systemic delivery of GalNAc siRNA conjugates, the liver can easily be targeted, opening up a plethora of diseases that can’t be treated locally. GAlNAcsiRNAs latch onto asialoglycoprotein receptors (ASGPR) commonly see on liver hepatocytes. ASGPRs transport the GAlNAcsiRNAs into the endosome through clathrin-mediated endocytosis. The conjugates then escape the endosome, bind with RISC, induce a robust interference in vivo and mediate targeted gene silencing. RISC eventually cleaves the troublesome mRNA and stops production of the diseased protein.GAlNAcsiRNA conjugates are the answer for an effective delivery system in RNA interference, and the same can be replicated to use in other tissues of the body.Although in the beginning, siRNA was predominantly available only in vitro, now, in vivo siRNA can be delivered too.

The delivery of siRNA has always been the crux of the issue. The shift from lipid nanoparticle (LNP) approach was important to harness the true power of RNA interference.This technology for GAlNAc delivery has shown repeatability in the sense that same performances have been observed across all genes in the liver. It seems to have a high therapeutic index, and for the patients’ benefit, it can be taken as sub-cutaneous injections, instead of intra-venous.

Even with such tremendous advancements, it will be a long while before the power of short-interfering RNA (siRNA) can be fully understood.

For any kind of tools in RNA interference, Advirna is your go-to place. From starter kits to validated sdRNAs, RNAi screens, transfection controls, in vivo RNAi and even COVID-siRNAs, they’ve got it all. Get in touch with Advirna for innovative solutions in RNA interference.