RNA Therapeutics - Research and Clinical Advancements

Abstract

RNA therapeutics involve the use of coding RNA such as mRNA as well as non-coding RNAs such as small interfering RNAs (siRNA), antisense oligonucleotides (ASO) to target mRNA, aptamers, ribozymes, and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR/Cas) endonuclease to target proteins and DNA. Due to their diverse targeting ability and research in RNA modification and delivery systems, RNA-based formulations have emerged as suitable treatment options for many diseases. Therefore, in this article, we have summarized different RNA therapeutics, their targeting strategies, and clinical progress for various diseases as well as limitations; so that it might help researchers formulate new and advanced RNA therapeutics for various diseases. Additionally, U.S. Food and Drug Administration (USFDA)-approved RNA-based therapeutics have also been discussed.

Lipid-Based Nanocarriers in Renal RNA Therapy

“…The current principle of RNA therapy involves the use of both coding and non-coding RNAs. There are five known types of therapeutic RNAs that are classified by their mode of action: (1) RNAs that inhibit RNA activity (miRNAs, siRNAs, antisense RNAs), (2) RNAs that target proteins (RNA aptamers), (3) RNAs that reprogram genetic information (trans-splicing ribozyme), (4) RNAs that encode therapeutic proteins (mRNAs) and (5) DNA-modifying CRISPR guide RNAs (gRNAs) [ 13 ]. The initial use of RNA as a form of therapy employed chemically synthesised antisense oligonucleotides [ 12 ].…”

“…These include QPI-1002 and NOX-E36 (Emamticap pegol). QPI-1002 uses an siRNA to target the p53 gene and is currently in phase I and II trials for acute renal failure and AKI, respectively [ 13 ]. NOX-E36 is an RNA aptamer targeting the C-C motif ligand 2, currently in phase II trials for type 2 diabetes mellitus and albuminuria [ 6 , 13 ].…”

“…QPI-1002 uses an siRNA to target the p53 gene and is currently in phase I and II trials for acute renal failure and AKI, respectively [ 13 ]. NOX-E36 is an RNA aptamer targeting the C-C motif ligand 2, currently in phase II trials for type 2 diabetes mellitus and albuminuria [ 6 , 13 ]. Another drug is one developed for Alport nephropathy, a genetic disorder characterised by chronic glomerulonephritis that progresses to end-stage renal disease in young adults.…”

Trimethyl-Chitosan Coated Gold Nanoparticles Enhance Delivery, Cellular Uptake and Gene Silencing Effect of EGFR-siRNA in Breast Cancer Cells

“…Small interfering RNA (siRNA), as a post transcriptional regulation of gene expression, has been introduced for fundamental treatment of mutant genes in cancer. siRNAs are double-stranded non-coding RNAs generally between 20 and 25 base pairs in length that can interact with the RNA-induced silencing complex (RISC), to degrade and cleave a complementary mRNA ( Feng et al, 2021 ). Although many studies have shown specific gene silencing using siRNA, its delivery in vivo can be challenging due to various biological barriers.…”

RNA Therapeutic Options to Manage Aberrant Signaling Pathways in Hepatocellular Carcinoma: Dream or Reality?

“…A wide range of novel HCC therapeutics have been developed and tested over the last two decades, including molecular targeted therapy, protein antibodies, targeted radionucleotide therapy, and epigenetic therapy. Other HCC therapies include immunotherapy, immune-cell therapy, differentiation strategy and RNA interference (RNAi) ( 2 ). Despite these advances a cure is yet to be developed and to date survival time has only been modestly extended ( 3 ).…”