Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells

Sijia Yi; Sun-Young Kim; Michael P. Vincent; Simseok A. Yuk; Sharan Bobbala; Fanfan Du; Evan Alexander Scott

iScience (Jul 2022)

Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells

Sijia Yi,
Sun-Young Kim,
Michael P. Vincent,
Simseok A. Yuk,
Sharan Bobbala,
Fanfan Du,
Evan Alexander Scott

Affiliations

Sijia Yi: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
Sun-Young Kim: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA; SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Republic of Korea
Michael P. Vincent: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
Simseok A. Yuk: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
Sharan Bobbala: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA; SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Republic of Korea; Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26505, USA; Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA; Department of Microbiology-Immunology, Northwestern University, Chicago, IL 60611, USA
Fanfan Du: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
Evan Alexander Scott: Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA; Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA; Department of Microbiology-Immunology, Northwestern University, Chicago, IL 60611, USA; Corresponding author

Journal volume & issue: Vol. 25, no. 7
p. 104555

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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