Optimizing mRNA-Loaded Lipid Nanoparticles as a Potential Tool for Protein-Replacement Therapy
-д хадгалсан:
| -д хэвлэсэн: | Pharmaceutics vol. 16, no. 6 (2024), p. 771 |
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| Үндсэн зохиолч: | |
| Бусад зохиолчид: | , , , , , , , , , , |
| Хэвлэсэн: |
MDPI AG
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| Нөхцлүүд: | |
| Онлайн хандалт: | Citation/Abstract Full Text + Graphics Full Text - PDF |
| Шошгууд: |
Шошго байхгүй, Энэхүү баримтыг шошголох эхний хүн болох!
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MARC
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| 024 | 7 | |a 10.3390/pharmaceutics16060771 |2 doi | |
| 035 | |a 3072643236 | ||
| 045 | 2 | |b d20240101 |b d20241231 | |
| 084 | |a 231549 |2 nlm | ||
| 100 | 1 | |a Gambaro, Rocío |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.) | |
| 245 | 1 | |a Optimizing mRNA-Loaded Lipid Nanoparticles as a Potential Tool for Protein-Replacement Therapy | |
| 260 | |b MDPI AG |c 2024 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Lipid nanoparticles (LNPs) tailored for mRNA delivery were optimized to serve as a platform for treating metabolic diseases. Four distinct lipid mixes (LMs) were formulated by modifying various components: LM1 (ALC-0315/DSPC/Cholesterol/ALC-0159), LM2 (ALC-0315/DOPE/Cholesterol/ALC-0159), LM3 (ALC-0315/DSPC/Cholesterol/DMG-PEG2k), and LM4 (DLin-MC3-DMA/DSPC/Cholesterol/ALC-0159). LNPs exhibited stability and homogeneity with a mean size of 75 to 90 nm, confirmed by cryo-TEM and SAXS studies. High mRNA encapsulation (95–100%) was achieved. LNPs effectively delivered EGFP-encoding mRNA to HepG2 and DC2.4 cell lines. LNPs induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs), revealing that LM1, LM2, and LM4 induced 1.5- to 4-fold increases in IL-8, TNF-α, and MCP-1 levels, while LM3 showed minimal changes. Reporter mRNA expression was observed in LNP-treated PBMCs. Hemotoxicity studies confirmed formulation biocompatibility with values below 2%. In vivo biodistribution in mice post intramuscular injection showed significant mRNA expression, mainly in the liver. The modification of LNP components influenced reactogenicity, inflammatory response, and mRNA expression, offering a promising platform for selecting less reactogenic carriers suitable for repetitive dosing in metabolic disease treatment. | |
| 651 | 4 | |a Switzerland | |
| 651 | 4 | |a United States--US | |
| 651 | 4 | |a Canada | |
| 651 | 4 | |a Germany | |
| 653 | |a Vaccines | ||
| 653 | |a Electrons | ||
| 653 | |a Lipids | ||
| 653 | |a Polyethylene glycol | ||
| 653 | |a Coronaviruses | ||
| 653 | |a Immune system | ||
| 653 | |a Metabolic disorders | ||
| 653 | |a Proteins | ||
| 700 | 1 | |a Ignacio Rivero Berti |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.); CINDEFI—Centro de Investigación y Desarrollo en Fermentaciones Industriales, Laboratorio de Nanobiomateriales (Universidad Nacional de La Plata (UNLP)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) LA PLATA), Facultad de Ciencias Exactas UNLP, La Plata 1900, Buenos Aires, Argentina | |
| 700 | 1 | |a Limeres, María José |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.) | |
| 700 | 1 | |a Huck-Iriart, Cristián |u Instituto de Tecnologías Emergentes y Ciencias Aplicadas (ITECA), Universidad Nacional de San Martín (UNSAM)-CONICET, Escuela de Ciencia y Tecnología (ECyT), Laboratorio de Cristalografía Aplicada (LCA), Campus Miguelete, San Martín 1650, Buenos Aires, Argentina; <email>chuck@cells.es</email>; ALBA Synchrotron Light Source, Carrer de la Llum 2–26, Cerdanyola del Vallès, 08290 Barcelona, Spain | |
| 700 | 1 | |a Svensson, Malin |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.) | |
| 700 | 1 | |a Fraude, Silvia |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.) | |
| 700 | 1 | |a Pretsch, Leah |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.) | |
| 700 | 1 | |a Si, Shutian |u Max Planck Institute for Polymer Research, Department of Physical Chemistry of Polymers, Ackermannweg 10, 55128 Mainz, Germany; <email>sis2@mpip-mainz.mpg.de</email> (S.S.); <email>lieberw@mpip-mainz.mpg.de</email> (I.L.) | |
| 700 | 1 | |a Lieberwirth, Ingo |u Max Planck Institute for Polymer Research, Department of Physical Chemistry of Polymers, Ackermannweg 10, 55128 Mainz, Germany; <email>sis2@mpip-mainz.mpg.de</email> (S.S.); <email>lieberw@mpip-mainz.mpg.de</email> (I.L.) | |
| 700 | 1 | |a Gehring, Stephan |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.) | |
| 700 | 1 | |a Cacicedo, Maximiliano |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.) | |
| 700 | 1 | |a Germán Abel Islan |u Children’s Hospital, University Medical Center of the Johannes, Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; <email>gambaror@uni-mainz.de</email> (R.G.); <email>ignaciob@uni-mainz.de</email> (I.R.B.); <email>mj.limeres@uni-mainz.de</email> (M.J.L.); <email>malin.svensson@uni-mainz.de</email> (M.S.); <email>fraudesi@uni-mainz.de</email> (S.F.); <email>pretsch@uni-mainz.de</email> (L.P.); <email>stephan.gehring@uni-mainz.de</email> (S.G.); CINDEFI—Centro de Investigación y Desarrollo en Fermentaciones Industriales, Laboratorio de Nanobiomateriales (Universidad Nacional de La Plata (UNLP)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) LA PLATA), Facultad de Ciencias Exactas UNLP, La Plata 1900, Buenos Aires, Argentina | |
| 773 | 0 | |t Pharmaceutics |g vol. 16, no. 6 (2024), p. 771 | |
| 786 | 0 | |d ProQuest |t Research Library | |
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