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A New Strategy for Nucleic Acid Delivery and Protein Expression Using Biocompatible Nanohydrogels of Predefined Sizes
We have developed new formulations of nanohydrogels (NHGs) complexed with DNA devoid of cell toxicity, which, together with their tuned sizes, makes them of great interest for delivering DNA/RNA for foreign protein expression. Transfection results demonstrate that, unlike classical lipo/polyplexes,...
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Published in: | Pharmaceutics 2023-03, Vol.15 (3), p.961 |
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description | We have developed new formulations of nanohydrogels (NHGs) complexed with DNA devoid of cell toxicity, which, together with their tuned sizes, makes them of great interest for delivering DNA/RNA for foreign protein expression. Transfection results demonstrate that, unlike classical lipo/polyplexes, the new NHGs can be incubated indefinitely with cells without apparent cellular toxicity, resulting in the high expression of foreign proteins for long periods of time. Although protein expression starts with a delay as compared to classical systems, it is sustained for a long period of time, even after passing cells without observation of toxicity. A fluorescently labelled NHG used for gene delivery was detected inside cells very early after incubation, but the protein expression was delayed by many days, demonstrating that there is a time-dependent release of genes from the NHGs. We suggest that this delay is due to the slow but continuous release of DNA from the particles concomitantly with slow but continuous protein expression. Additionally, results obtained after the in vivo administration of m-Cherry/NHG complexes indicated a delayed but prolonged expression of the marker gene in the tissue of administration. Overall, we have demonstrated gene delivery and foreign protein expression using GFP and m-Cherry marker genes complexed with biocompatible nanohydrogels. |
doi_str_mv | 10.3390/pharmaceutics15030961 |
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Transfection results demonstrate that, unlike classical lipo/polyplexes, the new NHGs can be incubated indefinitely with cells without apparent cellular toxicity, resulting in the high expression of foreign proteins for long periods of time. Although protein expression starts with a delay as compared to classical systems, it is sustained for a long period of time, even after passing cells without observation of toxicity. A fluorescently labelled NHG used for gene delivery was detected inside cells very early after incubation, but the protein expression was delayed by many days, demonstrating that there is a time-dependent release of genes from the NHGs. We suggest that this delay is due to the slow but continuous release of DNA from the particles concomitantly with slow but continuous protein expression. Additionally, results obtained after the in vivo administration of m-Cherry/NHG complexes indicated a delayed but prolonged expression of the marker gene in the tissue of administration. Overall, we have demonstrated gene delivery and foreign protein expression using GFP and m-Cherry marker genes complexed with biocompatible nanohydrogels.</description><identifier>ISSN: 1999-4923</identifier><identifier>EISSN: 1999-4923</identifier><identifier>DOI: 10.3390/pharmaceutics15030961</identifier><identifier>PMID: 36986821</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acids ; Alzheimer's disease ; Biocompatibility ; cationic nanohydrogels ; Cell culture ; Cell growth ; Cloning ; Dosage and administration ; Gels (Pharmacy) ; Gene expression ; Gene therapy ; Lipids ; Materials ; Microscopy ; Nanomedicine ; Nanoparticles ; non-viral gene delivery ; Plasmids ; polymerization ; Polymers in medicine ; Proteins ; self-assembly ; Software ; Structure</subject><ispartof>Pharmaceutics, 2023-03, Vol.15 (3), p.961</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Transfection results demonstrate that, unlike classical lipo/polyplexes, the new NHGs can be incubated indefinitely with cells without apparent cellular toxicity, resulting in the high expression of foreign proteins for long periods of time. Although protein expression starts with a delay as compared to classical systems, it is sustained for a long period of time, even after passing cells without observation of toxicity. A fluorescently labelled NHG used for gene delivery was detected inside cells very early after incubation, but the protein expression was delayed by many days, demonstrating that there is a time-dependent release of genes from the NHGs. We suggest that this delay is due to the slow but continuous release of DNA from the particles concomitantly with slow but continuous protein expression. Additionally, results obtained after the in vivo administration of m-Cherry/NHG complexes indicated a delayed but prolonged expression of the marker gene in the tissue of administration. Overall, we have demonstrated gene delivery and foreign protein expression using GFP and m-Cherry marker genes complexed with biocompatible nanohydrogels.</description><subject>Acids</subject><subject>Alzheimer's disease</subject><subject>Biocompatibility</subject><subject>cationic nanohydrogels</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cloning</subject><subject>Dosage and administration</subject><subject>Gels (Pharmacy)</subject><subject>Gene expression</subject><subject>Gene therapy</subject><subject>Lipids</subject><subject>Materials</subject><subject>Microscopy</subject><subject>Nanomedicine</subject><subject>Nanoparticles</subject><subject>non-viral gene delivery</subject><subject>Plasmids</subject><subject>polymerization</subject><subject>Polymers in medicine</subject><subject>Proteins</subject><subject>self-assembly</subject><subject>Software</subject><subject>Structure</subject><issn>1999-4923</issn><issn>1999-4923</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>COVID</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptksFu1DAQhiMEolXpI4AsceGyYMdJHJ_QUgpUqhak0rM1scdZr7J2sJPC8vR42VJahC-2xv984xn_RfGc0decS_pmXEPcgsZ5cjqxmnIqG_aoOGZSykUlS_743vmoOE1pQ_PinLVcPi2OeCPbpi3ZcTEvyQq_k6spwoT9jtgQyWrWAzpNltoZ8h4Hd4NxR8Ab8iWGCZ0n5z_GiCm54Ml1cr4n71zQYTvC5LoByQp8WO9MDD0OiQSb89CgdR4NuXI_MT0rnlgYEp7e7ifF9Yfzr2efFpefP16cLS8XuubVtGgABNVcdgyYrWUp2s5yEHWFLZgOOzCGd7psQWttGddI64pTy6qOixJYw0-KiwPXBNioMbotxJ0K4NTvQIi9gphnOKAqTQVdW1ndClbxxoBggrOmYcKyUvM2s94eWOPcbdFo9HlmwwPowxvv1qoPN4pRWre5n0x4dUuI4duMaVJblzQOA3gMc1KlkGXN8mfyLH35j3QT5ujzrPYqJijLNvir6iF34LwNubDeQ9VSVFyIfeWsqg8qHUNKEe3dmxlVezup_9op57243_Bd1h_z8F89hspO</recordid><startdate>20230316</startdate><enddate>20230316</enddate><creator>Eswaran, Lakshmanan</creator><creator>Kazimirsky, Gila</creator><creator>Yehuda, Ronen</creator><creator>Byk, Gerardo</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PKEHL</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-7159-9837</orcidid></search><sort><creationdate>20230316</creationdate><title>A New Strategy for Nucleic Acid Delivery and Protein Expression Using Biocompatible Nanohydrogels of Predefined Sizes</title><author>Eswaran, Lakshmanan ; 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Additionally, results obtained after the in vivo administration of m-Cherry/NHG complexes indicated a delayed but prolonged expression of the marker gene in the tissue of administration. Overall, we have demonstrated gene delivery and foreign protein expression using GFP and m-Cherry marker genes complexed with biocompatible nanohydrogels.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36986821</pmid><doi>10.3390/pharmaceutics15030961</doi><orcidid>https://orcid.org/0000-0002-7159-9837</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acids Alzheimer's disease Biocompatibility cationic nanohydrogels Cell culture Cell growth Cloning Dosage and administration Gels (Pharmacy) Gene expression Gene therapy Lipids Materials Microscopy Nanomedicine Nanoparticles non-viral gene delivery Plasmids polymerization Polymers in medicine Proteins self-assembly Software Structure |
title | A New Strategy for Nucleic Acid Delivery and Protein Expression Using Biocompatible Nanohydrogels of Predefined Sizes |
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