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.
Highlights
There are five types of therapeutic RNAs, 1) RNAs that inhibit RNA activity. This includes the use of small interfering RNAs (siRNA), antisense RNAs, 2) RNAs that target proteins such as RNA aptamers, 3) RNAs that reprogram genetic information including trans-splicing ribozyme, 4) RNAs that encode therapeutic proteins, and 5) DNA modifying CRISPR guide RNAs (Sullenger and Nair, 2016)
The first-ever RNA therapy that was approved by the U.S. Food and Drug Administration (USFDA) is fomivirsen for the treatment of cytomegalovirus retinitis, a manifestation of DNA herpes cytomegalovirus (CMV), commonly seen in advanced acquired immunodeficiency syndrome (AIDS). (Port et al, 2017) siRNA-based therapeutics for hereditary transthyretin-mediated amyloidosis and acute hepatic porphyria (AHP) have been approved by USFDA
RNA-based therapeutics evolved into a potential possible intervention strategy in various diseases
Summary
The Human Genome Project (HGP) has revealed vast information about the human genome and has greatly enhanced its role in the development of biomedical research. (Lander et al, 2001; Wan et al, 2014; Lekka and Hall, 2018) As a result of advancements in next-generation sequencing technology, researchers have been able to reveal the role of some genetic factors in many diseases such as cancer, rheumatoid arthritis, Parkinson’s, and Alzheimer’s disease. (Kaczmarek et al, 2017) the results of many studies have revealed the important role of coding as well as non-coding RNAs (ncRNAs), such as microRNAs (miRNA), long ncRNA (lncRNA), circular RNA (circRNA), and small interfering RNAs (siRNAs) in various diseases. (Gao et al, 2020) This has provided potential insight into developing possible treatments of various diseases by introducing nucleic acids into the cell to control the expression of altered genes permanently or transiently. (Smith and Blomberg, 2017) due to the inherent instability of RNA, it is often required to be delivered to the target site, which can be addressed by improving delivery systems through various modifications. (Patil et al, 2019) As a result, many RNA-based therapeutics involving siRNAs, ASO, ribozymes, mRNA, aptamers, and CRISPR/Cas have been developed and are being tested for their potential as a possible intervention strategy in various diseases (Moss et al, 2019) such as heart diseases, neurological diseases (amyotrophic lateral sclerosis (ALS), Alzheimer’s), and cancers. (Bekris and Leverenz, 2015; Reddy and Miller, 2015; De Majo and De Windt, 2018; Lei et al, 2019) In this review, we have summarized the clinical progress of siRNA, RNA ASO, RNA aptamers, ribozyme, mRNAs, and CRISPR guide RNAs (gRNAs) as RNA therapeutics to control gene expression through RNA, DNA, and protein. (Patil et al, 2019) As a result, many RNA-based therapeutics involving siRNAs, ASO, ribozymes, mRNA, aptamers, and CRISPR/Cas have been developed and are being tested for their potential as a possible intervention strategy in various diseases (Moss et al, 2019) such as heart diseases, neurological diseases (amyotrophic lateral sclerosis (ALS), Alzheimer’s), and cancers. (Bekris and Leverenz, 2015; Reddy and Miller, 2015; De Majo and De Windt, 2018; Lei et al, 2019) In this review, we have summarized the clinical progress of siRNA, RNA ASO, RNA aptamers, ribozyme, mRNAs, and CRISPR guide RNAs (gRNAs) as RNA therapeutics to control gene expression through RNA, DNA, and protein. The currently USFDAapproved RNA-based drugs and their future potential are discussed
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