Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells
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 sy...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222008276 |
| _version_ | 1818248551510048768 |
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| author | Sijia Yi Sun-Young Kim Michael P. Vincent Simseok A. Yuk Sharan Bobbala Fanfan Du Evan Alexander Scott |
| author_facet | Sijia Yi Sun-Young Kim Michael P. Vincent Simseok A. Yuk Sharan Bobbala Fanfan Du Evan Alexander Scott |
| author_sort | Sijia Yi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T15:22:24Z |
| format | Article |
| id | doaj.art-d432c22450994663a654c2b64e717126 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-12T15:22:24Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d432c22450994663a654c2b64e7171262022-12-22T00:20:21ZengElsevieriScience2589-00422022-07-01257104555Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cellsSijia Yi0Sun-Young Kim1Michael P. Vincent2Simseok A. Yuk3Sharan Bobbala4Fanfan Du5Evan Alexander Scott6Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USADepartment 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 KoreaDepartment of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USADepartment of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USADepartment 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, USADepartment of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222008276Health sciencesDrug delivery systemBiological sciencesImmunologyBiotechnology |
| spellingShingle | Sijia Yi Sun-Young Kim Michael P. Vincent Simseok A. Yuk Sharan Bobbala Fanfan Du Evan Alexander Scott Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells iScience Health sciences Drug delivery system Biological sciences Immunology Biotechnology |
| title | Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells |
| title_full | Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells |
| title_fullStr | Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells |
| title_full_unstemmed | Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells |
| title_short | Dendritic peptide-conjugated polymeric nanovectors for non-toxic delivery of plasmid DNA and enhanced non-viral transfection of immune cells |
| title_sort | dendritic peptide conjugated polymeric nanovectors for non toxic delivery of plasmid dna and enhanced non viral transfection of immune cells |
| topic | Health sciences Drug delivery system Biological sciences Immunology Biotechnology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222008276 |
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