Journal
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 16
Volume 16, Issue -, Pages 347-370Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-bioeng-071813-105119
Keywords
siRNA delivery; nanoparticle; gene therapy; stability; intracellular trafficking
Categories
Funding
- NCI NIH HHS [U54CA151838] Funding Source: Medline
- NHLBI NIH HHS [HL109442] Funding Source: Medline
- NIAID NIH HHS [AI096395] Funding Source: Medline
- NIBIB NIH HHS [EB015000, EB013274-01A1, EB015152] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [U54CA151838] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL109442] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R21EB015152, R21EB013274] Funding Source: NIH RePORTER
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Inhibiting specific gene expression by short interfering RNA (siRNA) offers a new therapeutic strategy to tackle many diseases, including cancer, metabolic disorders, and viral infections, at the molecular level. The macromolecular and polar nature of siRNA hinders its cellular access to exert its effect. Nanoparticulate delivery systems can promote efficient intracellular delivery. Despite showing promise in many preclinical studies and potential in some clinical trials, siRNA has poor delivery efficiency, which continues to demand innovations, from carrier design to formulation, in order to overcome transport barriers. Previous findings for optimal plasmid DNA delivery cannot be generalized to siRNA delivery owing to significant discrepancy in size and subtle differences in chain flexibility between the two types of nucleic acids. In this review, we highlight the recent advances in improving the stability of siRNA nanoparticles, understanding their intracellular trafficking and release mechanisms, and applying judiciously the promising formulations to disease models.
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