PLGA and PEG-PLGA from PolySciTech used in development of CRISPR technique for gene editing in vascular system

 

The ability to deliver genetic material and make edits to existing cells holds great promise for treating a wide variety of diseases. Recently, researchers at the Lurie Hospital of Chicago and Northwestern University used PLGA (Cat# AP121) and PEG-PLGA (Cat# AK026) from PolySciTech (www.polyscitech.com) to create nanoparticles for delivery of plasmid DNA to vascular components. This research holds promise to improve treatment against cardiovascular diseases by modifying genes to correct disease states. Read more: Zhang, Xianming, Hua Jin, Xiaojia Huang, Birendra Chaurasiya, Daoyin Dong, Thomas P. Shanley, and You-Yang Zhao. "Robust genome editing in adult vascular endothelium by nanoparticle delivery of CRISPR-Cas9 plasmid DNA." Cell reports 38, no. 1 (2022): 110196. https://www.sciencedirect.com/science/article/pii/S2211124721017009

“Highlights: PPP i.v. exhibits excellent biodistribution without specific liver accumulation. PPP efficiently delivers plasmid DNA in vivo targeting vascular ECs. PPP delivery of CRISPR plasmid decreases 80% protein in cardiopulmonary vascular ECs. The system induces genome editing of two genes in ECs without limitation on plasmid size. Abstract: Vascular endothelium plays a crucial role in vascular homeostasis and tissue fluid balance. To target endothelium for robust genome editing, we developed poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-b-PLGA) copolymer-based nanoparticle formulated with polyethyleneimine. A single i.v. administration of mixture of nanoparticles and plasmid DNA expressing Cas9 controlled by CDH5 promoter and guide RNA (U6 promoter) induced highly efficient genome editing in endothelial cells (ECs) of the vasculatures, including lung, heart, aorta, and peripheral vessels in adult mice. Western blotting and immunofluorescent staining demonstrated an ∼80% decrease of protein expression selectively in ECs, resulting in a phenotype similar to that of genetic knockout mice. Nanoparticle delivery of plasmid DNA could induce genome editing of two genes or genome editing and transgene expression in ECs simultaneously. Thus, nanoparticle delivery of plasmid DNA is a powerful tool to rapidly and efficiently alter expression of gene(s) in ECs for cardiovascular research and potential gene therapy. Keywords: CRISPR-Cas9 cardiovascular disease endothelial cell genome editing nanoparticle non-viral CRISPR delivery gene delivery gene therapy endothelium targeting lung diseases”