Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells
Year: 2022
Type: article
Abstract: Plasmid DNA (pDNA) transfection is advantageous for gene therapies requiring larger genetic elements, including "all-in-one" CRISPR/Cas9 plasmids, but is limited by toxicity as well as poor intracellular release and transfection efficiency in immune cell populations. Here, we developed a synthetic non-viral gene delivery platform composed of poly(ethylene glycol)- b -poly(propylene sulfide) copolymers linked to a cationic dendritic peptide (DP) via a reduceable bond, PEG- b -PPS-ss-DP (PPDP). A library of self-assembling PPDP polymers was synthesized and screened to identify optimal constructs capable of transfecting macrophages with small (pCMV-DsRed, 4.6 kb) and large (pL-CRISPR.EFS.tRFP, 11.7 kb) plasmids. The optimized PPDP construct transfected macrophages, fibroblasts, dendritic cells, and T cells more efficiently and with less toxicity than a commercial Lipo2K reagent, regardless of pDNA size and under standard culture conditions in the presence of serum. The PPDP technology described herein is a stimuli-responsive polymeric nanovector that can be leveraged to meet diverse challenges in gene delivery.
Source: iScience
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funders: Northwestern University, Ministry of Science, ICT and Future Planning, National Research Foundation of Korea, National Institutes of Health, Materials Research Science and Engineering Center, Harvard University, National Heart, Lung, and Blood Institute, National Eye Institute, National Institute of Allergy and Infectious Diseases
Awards: G1497003984, G2243555408, G2845782492, Development of combination immunotherapies for atherosclerotic inflammation, Design and characterization of biomimetic nanobiomaterials to elicit CD1-restricted T cell responses during sub-unit vaccination, G6174092448, G7087147493, G801469781, G875283887
OpenAlex ID: W4283756763