Highly-Stablized Nanocapsules for siRNA Delivery

Tech ID: 23000 / UC Case 2010-904-0

Summary

UCLA scientists have developed novel nanocapsules that facilitate efficient siRNA delivery into cells. The invention represents a significant advancement in realizing therapeutics based on targeted reduction of gene expression.  

Background

Short interfering RNA (siRNA), possessing the unique capability to specifically knock down the undesired expression of genes, holds great promise as therapeutics for human diseases. However, its clinical applications are constrained by the lack of a delivery vehicle that is safe, stable, and efficient. To date, various delivery systems have been proposed, including cationic liposomes, cell-penetrating peptides (CPP), and cationic polymers. Cationic liposomes and lipids are used widely for in vitro studies with high effectiveness; however, their toxicity and low efficiency restrain in vivo application. For the CPP-based approach, siRNA-CPP complexed particles exhibit significantly improved delivery efficiency but remain generally unstable, particularly, against serum nucleases. For the cationic-polymer-based approach, siRNA is assembled with cationic polymers mainly through the electrostatic interactions, which improves intracellular delivery efficiency. However, like the CPP-based approach, such assembled systems are unstable, which may readily dissociate and release their siRNA payload before reaching the cytoplasm of the target cells. Therefore, in spite of such intensive efforts, the design and synthesis of an effective delivery vehicle for siRNA remains challenging.

Innovation

The novel capsulation method developed by UCLA scientists uniquely stabilizes siRNA molecules at a neutral pH, thereby preventing extracellular degradation in serum. In addition, the crosslinked polymerized shell of the nanocapsule degrades in acidic environments, like that found in late endosomes, allowing exclusive release of siRNA to occur within cells. These properties promote efficient delivery of therapeutically relevant concentrations of siRNA molecules. In practice, the proprietary nanoparticles exhibited greater knockdown of gene expression than lipofectamine in cells cultured with human serum. The results corroborate the promising utility of the nanoparticles for therapeutic siRNA delivery.   

Applications

·         Intracellular delivery of siRNA

o   Therapeutic applications 

o   Research reagents

Advantages

·         Protects siRNA from hydrolysis

·         Efficient cellular transduction of siRNA

·         Preferential intracellular release of siRNA payload

State Of Development

The nanoparticle components and capsulation process have been optimized and tested for delivery of siRNA molecules.  Proof-of-concept experiments have been performed in HEK293 cells in culture and in the presence of human serum.     

Patent Status

Country Type Number Dated Case
Canada Issued Patent 2,907,095 11/03/2020 2010-904
Australia Issued Patent 2018201179 03/26/2020 2010-904
United States Of America Issued Patent 10,568,844 02/25/2020 2010-904
Australia Issued Patent 2013231839 03/08/2018 2010-904
Japan Issued Patent 6283652 02/02/2018 2010-904
United States Of America Issued Patent 9,782,357 10/10/2017 2010-904
United States Of America Published Application 20200397712 12/24/2020 2010-904
 

Additional Patents Pending

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Inventors

  • Lu, Yunfeng

Other Information

Keywords

siRNA, nanoparticles, drug delivery, therapeutics, research reagents

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