A comprehensive update of siRNA delivery design strategies for targeted and effective gene silencing in gene therapy and other applications.

Expert Opin Drug Discov

Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University H3A 2B4, Montreal, Quebec, Canada.

Published: February 2023

AI Article Synopsis

  • RNA interference (RNAi) using small interfering RNA (siRNA) shows promise for treating genetic disorders but faces significant delivery challenges due to various barriers.
  • Strategies to enhance siRNA delivery include chemical modifications, bioconjugation with ligands, and nanotechnology-based systems like liposomes and nanoparticles.
  • Despite the established mechanism of siRNA as a gene silencer, effective therapeutic products remain limited, and there's an urgent need for improved delivery systems to target specific sites for treating diseases early on.

Article Abstract

Introduction: RNA interference (RNAi) using small interfering RNA (siRNA) is a promising strategy to control many genetic disorders by targeting the mRNA of underlying genes and degrade it. However, the delivery of siRNA to targeted organs is highly restricted by several intracellular and extracellular barriers.

Areas Covered: This review discusses various design strategies developed to overcome siRNA delivery obstacles. The applied techniques involve chemical modification, bioconjugation to specific ligands, and carrier-mediated strategies. Nanotechnology-based systems like liposomes, niosomes, solid lipid nanoparticles (SLNs), dendrimers, and polymeric nanoparticles (PNs) are also discussed.

Expert Opinion: Although the mechanism of siRNA as a gene silencer is well-established, only a few products are available as therapeutics. There is a great need to develop and establish siRNA delivery systems that protects siRNAs and delivers them efficiently to the desired sitesare efficient and capable of targeted delivery. Several diseases are reported to be controlled by siRNA at their early stages. However, their targeted delivery is a daunting challenge.

Download full-text PDF

Source
http://dx.doi.org/10.1080/17460441.2022.2155630DOI Listing

Publication Analysis

Top Keywords

sirna delivery
12
design strategies
8
targeted delivery
8
sirna
7
delivery
6
comprehensive update
4
update sirna
4
delivery design
4
targeted
4
strategies targeted
4

Similar Publications

Following myocardial infarction (MI), the accumulation of CD86-positive macrophages in the ischemic injury zone leads to secondary myocardial damage. Precise pharmacological intervention targeting this process remains challenging. This study engineered a nanotherapeutic delivery system with CD86-positive macrophage-specific targeting and ultrasound-responsive release capabilities.

View Article and Find Full Text PDF

Huntington's disease (HD) is a progressive neurodegenerative disease resulting from a mutation in the huntingtin (HTT) gene and characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Currently, no disease-modifying treatments are available. Recent research has developed therapeutic agents that may have the potential to directly target the disease pathology, such as gene silencing or clearing the mutant protein.

View Article and Find Full Text PDF

Co-delivery of antioxidants and siRNA-VEGF: promising treatment for age-related macular degeneration.

Drug Deliv Transl Res

January 2025

Pharmaceutical Research and Development, Ezequiel Dias Foundation, Rua Conde Pereira Carneiro 80, Gameleira, Belo Horizonte, CEP 30510-010, Minas Gerais, Brazil.

Current treatments for retinal disorders are anti-angiogenic agents, laser photocoagulation, and photodynamic therapies. These conventional treatments focus on reducing abnormal blood vessel formation in the retina, which, in a low-oxygen environment, can lead to harmful proliferation of endothelial cells. This results in dysfunctional, leaky blood vessels that cause retinal edema, hemorrhage, and vision loss.

View Article and Find Full Text PDF

Nanoparticle-mediated delivery of nucleic acids and proteins into intact plants has the potential to modify metabolic pathways and confer desirable traits in crops. Here we show that layered double hydroxide (LDH) nanosheets coated with lysozyme are actively taken up into the root tip, root hairs and lateral root junctions by endocytosis, and translocate via an active membrane trafficking pathway in plants. Lysozyme coating enhanced nanosheet uptake by (1) loosening the plant cell wall and (2) stimulating the expression of endocytosis and other membrane trafficking genes.

View Article and Find Full Text PDF

Gene therapy has evolved into a pivotal approach for treating genetic disorders, extending beyond traditional methods of directly repairing or replacing defective genes. Recent advancements in nucleic acid-based therapies-including mRNA, miRNA, siRNA, and DNA treatments have expanded the scope of gene therapy to include strategies that modulate protein expression and deliver functional genetic material without altering the genetic sequence itself. This review focuses on the innovative use of plant-derived nanovesicles (PDNVs) as a promising delivery system for these nucleic acids.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!