Technologies for controlled, local delivery of siRNA

Sarett, Samantha M.; Nelson, Christopher E.; Duvall, Craig L.

doi:10.1016/j.jconrel.2015.09.066

Cited by 70 publications

(52 citation statements)

References 200 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The most commonly used strategy is to directly inject the hydrogel intratumorally for release of nucleic acids into the tumor. The unique challenge nucleic acid delivery is penetration into the cell, and this is most commonly achieved by encapsulating nucleic acids in nanoparticles first, condensing these with cationic polymers to form polyplexes and modification of the nucleic acid to improve its cell penetration properties …”

Section: Hydrogel As Depot Systems For Improved Therapeutic Deliverymentioning

confidence: 99%

Hydrogels as Emerging Materials for Translational Biomedicine

Ke-min

Wang

Yong

et al. 2018

Advanced Therapeutics

View full text Add to dashboard Cite

Hydrogels have been extensively investigated as biomaterials because of their excellent biocompatibility, and recent developments such as 3D printing and the incorporation of dynamic crosslinks have advanced the field considerably. However, the next step of in vivo translational biomedicine requires an understanding of essential hydrogel properties so that they can be designed to overcome the challenges of the living environment. In this review, the stringent design criteria required for in vivo applications are highlighted and recent advances in the repair of organ tissues (heart, bone, eye, etc.) and the therapeutic delivery of bioactive molecules are described. Commercially available hydrogel systems that can be used for translational biomedicine are also discussed, as is the long and sometimes fraught journey from the laboratory to the clinic.The question then arises whether the next iteration of hydrogels can be designed for long-term applications in an in vivo environment with all its complicating agents and factors, and issues such as biodistribution and immune responses. [27][28][29][30] Hydrogels could be prone to dissociation by high shear forces, or the responsiveness to stimuli could be much less sensitive within the body. [31][32][33][34] In this review, we discuss the design of hydrogels for in vivo applications, including for use clinically and commercially. This is not a comprehensive review of the entire field of translational hydrogels, but concentrates on promising results in animal trials. The reader is referred to several reviews which offer a different perspective and provide more detailed information on injectable hydrogels, regenerative scaffolds, and therapeutic delivery. [2,11,24,[35][36][37][38][39]

show abstract

Section: Hydrogel As Depot Systems For Improved Therapeutic Deliverymentioning

confidence: 99%

Hydrogels as Emerging Materials for Translational Biomedicine

Ke-min

Wang

Yong

et al. 2018

Advanced Therapeutics

View full text Add to dashboard Cite

show abstract

“…In the latter, perfect binding of miRNA to mRNA leads to direct target mRNA cleavage. miRNA silencing pathways can be successfully recapitulated exogenously by introducing miRNA “mimics,” which are double‐stranded RNA molecules that can associate with RISC in the cytoplasm for gene silencing …”

Section: Introductionmentioning

confidence: 99%

Engineered Hydrogels for Local and Sustained Delivery of RNA‐Interference Therapies

Wang

Burdick

2016

Adv Healthcare Materials

View full text Add to dashboard Cite

It has been nearly two decades since RNA-interference (RNAi) was first reported. While there are no approved clinical uses, several promising phase II and III clinical trials suggest the great promise of RNAi therapeutics. One challenge for RNAi therapies is the controlled localization and sustained presentation to target tissues, to both overcome systemic toxicity concerns and to enhance in vivo efficacy. One approach that is emerging to address these limitations is the entrapment of RNAi molecules within hydrogels for local and sustained release. In these systems, nucleic acids are either delivered as siRNA conjugates or within nanoparticles. A plethora of hydrogels has been implemented using these approaches, including both traditional hydrogels that have already been developed for other applications and new hydrogels developed specifically for RNAi delivery. These hydrogels have been applied to various applications in vivo, including cancer, bone regeneration, inflammation and cardiac repair. This review will examine the design and implementation of such hydrogel RNAi systems and will cover the most recent applications of these systems.

show abstract

“…From a biomaterial point of view, RNAi-based gene therapy allows to diversify siRNA sequences without modifying the overall chemistry of the molecule, resulting in a highly versatile molecule targeting different host factors with the same delivery strategy. 7,8 Previous studies on the use of siRNAs have put emphasis on several advantages when working with such molecules. Firstly, using cocktails of different siRNAs targeting the same gene allows increasing the global siRNA concentration without reaching the threshold of off-target effects.…”

Section: Introductionmentioning

confidence: 99%

Composite vector formulation for multiple siRNA delivery as a host targeting antiviral in a cell culture model of hepatitis C virus (HCV) infection

et al. 2017

View full text Add to dashboard Cite

bceHepatitis C virus (HCV) infection is a major cause of chronic liver disease and cancer worldwide. RNA interference (RNAi)-based gene therapies have emerged recently as a promising tool to treat chronic viral infections. Indeed, small interfering RNAs (siRNAs) provide an opportunity to target host factors required for the viral life cycle. In this study, we evaluated a novel nanovector-based approach for siRNA delivery in a model of chronically infected hepatic cells. We designed original composite nanoparticles by coating the calcium phosphate core with siRNAs targeting HCV host-factors and pyridylthiourea-grafted polyethyleneimine (pPEI). Using combinations of different siRNAs, we observed an efficient and prolonged decrease of HCV replication. Moreover, we showed that the layer-by-layer technique of coating applied to our nanoparticles triggers a sequential release of siRNAs acting on different steps of the HCV life cycle.Together, our results demonstrate the efficacy of these nanoparticles for siRNA delivery and open new perspectives for antiviral therapies.

show abstract

Technologies for controlled, local delivery of siRNA

Cited by 70 publications

References 200 publications

Hydrogels as Emerging Materials for Translational Biomedicine

Hydrogels as Emerging Materials for Translational Biomedicine

Engineered Hydrogels for Local and Sustained Delivery of RNA‐Interference Therapies

Composite vector formulation for multiple siRNA delivery as a host targeting antiviral in a cell culture model of hepatitis C virus (HCV) infection

Contact Info

Product

Resources

About