Innovations in RNA therapeutics: a review of recent advances and emerging technologies

Nucleosides Nucleotides & Nucleic Acids, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 25

Published: Jan. 13, 2025

The field of biomedical science has witnessed another milestone with the advent RNA-based therapeutics. This review explores three major RNA molecules, namely: messenger (mRNA), interference technology (RNAi), and Antisense Oligonucleotide (ASO), analyses U.S. Food Drug Administration drugs from 14 pharmaceutical companies in terms targeted genes, diseases types, clinical trials status, mode delivery, year production. Many such are clinically approved or pending approval by (FDA) alongside other leading agencies. Regarding diseases, this article emphasizes cancer therapy, genetic viral infections, two categories drug delivery systems include vectors nanoparticles. Despite tremendous progress made, key issues associated these stability, off-target activities payloads, efficiency cellular uptake, innovative need for engineering techniques modifications. transformative potential therapeutics role technologies addressing needs, paving way a new era precision medicine.

Language: Английский

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RNA-based therapies: A cog in the wheel of lung cancer defense

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: March 19, 2021

Abstract Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung (NSCLC) and small (SCLC), remains the leading cause death worldwide. Despite recent advances in therapies, overall 5-year survival rate LC less than 20%. The efficacy current therapeutic approaches compromised by inherent or acquired drug-resistance severe off-target effects. Therefore, identification development innovative effective are critically desired for LC. RNA-mediated gene inhibition technologies was turning point field RNA biology. critical regulatory role different RNAs multiple pathways makes them rich source targets tools developing anticancer therapies. antisense sequences, short interfering (siRNAs), microRNAs (miRNAs miRs), anti-miRs, mRNA-based platforms holds great promise preclinical early clinical evaluation against In last decade, RNA-based therapies have substantially expanded tested trials malignancies, including This article describes understanding various aspects therapeutics, modern platforms, modifications, combinations with chemo-/immunotherapies that translational potential

Language: Английский

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Chemistry of Peptide-Oligonucleotide Conjugates: A Review

Molecules, Journal Year: 2021, Volume and Issue: 26(17), P. 5420 - 5420

Published: Sept. 6, 2021

Peptide-oligonucleotide conjugates (POCs) represent one of the increasingly successful albeit costly approaches to increasing cellular uptake, tissue delivery, bioavailability, and, thus, overall efficiency therapeutic nucleic acids, such as, antisense oligonucleotides and small interfering RNAs. This review puts subject chemical synthesis POCs into wider context problem acid drug cell-penetrating peptide structural types, mechanisms their intracellular transport, ways application, which include formation non-covalent complexes with (peptide additives) or covalent conjugation. The main strategies for are viewed in detail, conceptually divided (a) stepwise solid-phase approach (b) post-synthetic conjugation either solution on solid phase, especially by means various click chemistries. relative advantages disadvantages both discussed compared.

Language: Английский

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Tumor-suppressive circRHOBTB3 is excreted out of cells via exosome to sustain colorectal cancer cell fitness

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 11, 2022

Abstract Background & Aims To clarify the biological roles, circularization process and secretion pathway of circRHOBTB3 in colorectal cancer (CRC) progression. Methods We performed a comprehensive analysis circRNA levels serum exosomes from multiple types patients public databases verified higher level CRC sera versus healthy donors by RT-qPCR. Then, function was investigated vitro vivo. RNA-seq RNA pull-down assays together with mass spectrometry identified downstream signals binding proteins circRHOBTB3. Finally, Antisense oligonucleotides (ASOs) were designed to target elements for therapy. Results increased but downregulated tissue samples CRC, downregulation associated poor prognosis. Furthermore, acts tumor-suppressive repressing metabolic pathways, intracellular ROS production CRC. Several key discovered regulate exosomal secretion. Moreover, SNF8 that sorts into exosomes. Interestingly, we found cells could actively secrete more than normal cells. According sequence regulatory secretion, synthesized ASOs, which expression blocked More importantly, ASOs inhibit growth metastasis Conclusions plays role has be excreted out sustain cell fitness. targeting will become novel antitumor strategy.

Language: Английский

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Small Drugs, Huge Impact: The Extraordinary Impact of Antisense Oligonucleotides in Research and Drug Development

Molecules, Journal Year: 2022, Volume and Issue: 27(2), P. 536 - 536

Published: Jan. 15, 2022

Antisense oligonucleotides (ASOs) are an increasingly represented class of drugs. These small sequences nucleotides designed to precisely target other oligonucleotides, usually RNA species, and modified protect them from degradation by nucleases. Their specificity is due their sequence, so it possible any sequence that already known. molecules very versatile adaptable given chemistry can be custom manufactured. Based on the being used, activity may significantly change effects cell function phenotypes differ dramatically. While some will cause decay, others only bind act as a steric blocker. incredible versatility key manipulating several aspects nucleic acid well process, alter transcriptome profile specific type or tissue. For example, they used modify splicing mask sites target. The entire design rather than just essential ensuring ASO its Thus, vitally important ensure complete process drug testing taken into account. ASOs’ adaptability considerable advantage, over past decades has allowed multiple new drugs approved. This, in turn, had significant positive impact patient lives. Given current challenges presented COVID-19 pandemic, necessary find therapeutic strategies would complement vaccination efforts across globe. ASOs powerful tool virus provide paradigm. proof efficacy anti-viral agent long-standing, yet no molecule currently FDA approval. emergence widespread use vaccines during this health crisis might ideal opportunity develop first market. In review, we describe story ASOs, different characteristics chemistry, how translate research clinical tool.

Language: Английский

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