Cellular and Molecular Biology
Open Access

RNA interference; RNAi; siRNA; miRNA; lncRNA; gene silencing; therapeutics; delivery systems; cancer; neurodegenerative diseases; antiviral; CRISPR/Cas9

Introduction

RNA interference (RNAi) is a fundamental biological process offering an accessible overview of its core molecular mechanisms, including the roles of Dicer, RISC, and argonaute proteins in processing and executing gene silencing [10].

It discusses various applications of RNAi in biological research, biotechnology, and potential therapeutic contexts [10].

The authors also consider the future prospects of RNAi, acknowledging both its immense potential and the ongoing challenges in translating laboratory discoveries into widespread clinical success [10].

The article discusses the significant progress in RNA interference (RNAi)-based therapeutics, from foundational discoveries to current clinical applications [3].

It highlights how RNAi technology offers precise gene silencing for previously 'undruggable' targets and explores advanced delivery strategies, including lipid nanoparticles and conjugate delivery, that are crucial for successful clinical translation [3].

The authors outline the pipeline of RNAi drugs, pointing towards promising future developments across various disease areas [3].

This article offers a comprehensive overview of small interfering RNAs (siRNAs), highlighting their fundamental mechanisms in gene silencing and their increasing utility as therapeutic agents [1].

It delves into the current landscape of siRNA-based drugs, addressing achievements in clinical trials and the challenges in delivery systems, stability, and off-target effects [1].

The authors project future directions for siRNA applications, emphasizing novel modifications and advanced delivery platforms to enhance efficacy and safety [1].

This review provides an updated perspective on microRNA (miRNA) biogenesis, tracing the complex pathway from primary miRNA transcription to mature miRNA formation, involving key enzymes like Drosha and Dicer [2].

It also elaborates on the diverse functional roles of miRNAs in regulating gene expression post-transcriptionally, influencing crucial biological processes such as cell proliferation, differentiation, and apoptosis, with implications for disease pathogenesis [2].

This article elucidates the intricate connection between long non-coding RNAs (lncRNAs) and the RNA interference (RNAi) pathway [6].

It details how lncRNAs can regulate gene expression through various mechanisms, including acting as sponges for miRNAs, modulating the activity of RNAi machinery components, or guiding epigenetic modifications [6].

Understanding these interactions is crucial for comprehending complex gene regulatory networks and exploring lncRNA-RNAi interplay as therapeutic targets in diseases like cancer [6].

The article reviews recent advancements in delivery strategies for RNA interference-based therapeutics, a critical hurdle for their clinical translation [7].

It explores various innovative delivery vehicles, including nanocarriers, viral vectors, and chemical modifications, designed to protect RNAi agents from degradation, ensure efficient cellular uptake, and minimize off-target effects [7].

The authors also highlight successful therapeutic applications emerging from these improved delivery systems across diverse pathological conditions [7].

This paper investigates RNA interference as a potent antiviral strategy, leveraging the host cell's natural RNAi machinery to inhibit viral replication by targeting viral RNA or host factors essential for infection [4].

It details various approaches, including the use of siRNAs and miRNAs, to combat a range of viruses, from common respiratory pathogens to emerging threats [4].

The authors discuss both the promise and challenges associated with developing effective and safe RNAi-based antiviral therapies [4].

This review highlights recent advancements in RNA interference-based gene therapy specifically for cancer treatment [5].

It explores how RNAi can selectively silence oncogenes, restore tumor suppressor genes, or target genes involved in drug resistance and metastasis [5].

The article provides insights into novel delivery systems, such as nanoparticles and viral vectors, designed to enhance the specificity and efficacy of RNAi therapeutics in various cancer types, paving the way for more targeted and personalized oncology approaches [5].

This comprehensive review examines RNA interference as a promising therapeutic strategy for combating neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's [8].

It discusses how RNAi can selectively silence mutant genes, reduce aggregation of toxic proteins, or modify disease-related pathways [8].

The authors explore the challenges of delivering RNAi agents across the blood-brain barrier and recent progress in overcoming these obstacles to develop effective treatments for central nervous system disorders [8].

This article explores the synergistic potential of combining CRISPR/Cas9 gene editing with RNA interference technologies for enhanced genetic manipulation and therapeutic applications [9].

It discusses how the precise targeting of CRISPR can complement the reversible gene silencing of RNAi, offering a powerful toolkit for both basic research and disease intervention [9].

The authors highlight applications ranging from more robust gene knockdowns and functional genomics studies to advanced strategies for treating genetic disorders and cancers [9].

Description

RNA interference (RNAi) is a fundamental biological process detailing its core molecular mechanisms, including the roles of Dicer, RISC, and argonaute proteins in processing and executing gene silencing [10]. It discusses various applications of RNAi in biological research, biotechnology, and potential therapeutic contexts [10]. This article offers a comprehensive overview of small interfering RNAs (siRNAs), highlighting their fundamental mechanisms in gene silencing and their increasing utility as therapeutic agents [1]. This review provides an updated perspective on microRNA (miRNA) biogenesis, tracing the complex pathway from primary miRNA transcription to mature miRNA formation, involving key enzymes like Drosha and Dicer [2]. It also elaborates on the diverse functional roles of miRNAs in regulating gene expression post-transcriptionally, influencing crucial biological processes such as cell proliferation, differentiation, and apoptosis, with implications for disease pathogenesis [2].

The article discusses the significant progress in RNA interference (RNAi)-based therapeutics, from foundational discoveries to current clinical applications [3]. It highlights how RNAi technology offers precise gene silencing for previously 'undruggable' targets and explores advanced delivery strategies, including lipid nanoparticles and conjugate delivery, that are crucial for successful clinical translation [3]. The article reviews recent advancements in delivery strategies for RNA interference-based therapeutics, a critical hurdle for their clinical translation [7]. It explores various innovative delivery vehicles, including nanocarriers, viral vectors, and chemical modifications, designed to protect RNAi agents from degradation, ensure efficient cellular uptake, and minimize off-target effects [7].

This paper investigates RNA interference as a potent antiviral strategy, leveraging the host cell's natural RNAi machinery to inhibit viral replication by targeting viral RNA or host factors essential for infection [4]. It details various approaches, including the use of siRNAs and miRNAs, to combat a range of viruses, from common respiratory pathogens to emerging threats [4]. This review highlights recent advancements in RNA interference-based gene therapy specifically for cancer treatment [5]. It explores how RNAi can selectively silence oncogenes, restore tumor suppressor genes, or target genes involved in drug resistance and metastasis [5].

This comprehensive review examines RNA interference as a promising therapeutic strategy for combating neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's [8]. It discusses how RNAi can selectively silence mutant genes, reduce aggregation of toxic proteins, or modify disease-related pathways [8]. This article elucidates the intricate connection between long non-coding RNAs (lncRNAs) and the RNA interference (RNAi) pathway [6]. It details how lncRNAs can regulate gene expression through various mechanisms, including acting as sponges for miRNAs, modulating the activity of RNAi machinery components, or guiding epigenetic modifications [6].

This article explores the synergistic potential of combining CRISPR/Cas9 gene editing with RNA interference technologies for enhanced genetic manipulation and therapeutic applications [9]. It discusses how the precise targeting of CRISPR can complement the reversible gene silencing of RNAi, offering a powerful toolkit for both basic research and disease intervention [9]. The authors highlight applications ranging from more robust gene knockdowns and functional genomics studies to advanced strategies for treating genetic disorders and cancers [9]. The authors outline the pipeline of RNAi drugs, pointing towards promising future developments across various disease areas [3]. The authors also consider the future prospects of RNAi, acknowledging both its immense potential and the ongoing challenges in translating laboratory discoveries into widespread clinical success [10].

Conclusion

RNA interference (RNAi) represents a powerful gene silencing mechanism, with various forms like small interfering RNAs (siRNAs) and microRNAs (miRNAs) playing crucial regulatory roles. siRNAs are gaining traction as therapeutic agents, with ongoing clinical trials addressing challenges in delivery, stability, and off-target effects. Future advancements in siRNA applications are expected through novel modifications and enhanced delivery platforms. miRNAs, central to post-transcriptional gene expression, influence essential biological processes such as cell proliferation and apoptosis, with significant implications for disease pathogenesis. The therapeutic potential of RNAi is substantial, offering precise gene silencing for previously challenging targets, moving from foundational discoveries to clinical applications. Advanced delivery strategies, including lipid nanoparticles and conjugate delivery, are vital for this translation. RNAi also serves as a potent antiviral strategy, leveraging host machinery to inhibit viral replication, though developing effective and safe therapies presents challenges. In cancer treatment, RNAi-based gene therapy shows promise by selectively silencing oncogenes or restoring tumor suppressor functions, utilizing novel delivery systems like nanoparticles and viral vectors. Beyond siRNAs and miRNAs, long non-coding RNAs (lncRNAs) intricately connect with the RNAi pathway, regulating gene expression by acting as miRNA sponges or modulating RNAi machinery. This interplay is key for understanding gene networks and identifying therapeutic targets. Delivery strategies remain a critical hurdle for RNAi therapeutics, with nanocarriers, viral vectors, and chemical modifications aimed at protecting agents and ensuring efficient uptake. RNAi is also a potential therapeutic strategy for neurodegenerative diseases, targeting mutant genes and toxic proteins, despite blood-brain barrier delivery challenges. The synergistic combination of CRISPR/Cas9 gene editing with RNAi offers enhanced genetic manipulation, providing a powerful toolkit for robust gene knockdowns and advanced strategies for genetic disorders and cancers. Overall, RNAi's core molecular mechanisms, involving Dicer, RISC, and argonaute proteins, underpin its wide applications in research, biotechnology, and therapeutics, despite ongoing challenges in clinical translation.

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