Serum Nuclease Susceptibility of mRNA Cargo in Condensed Polyplexes
| العنوان: | Serum Nuclease Susceptibility of mRNA Cargo in Condensed Polyplexes |
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| المؤلفون: | Sanyogitta Puri, Meilyn Sylvestre, Yilong Cheng, Heather H. Gustafson, Suzie H. Pun, Albert Yen |
| المصدر: | Molecular Pharmaceutics. 15:2268-2276 |
| بيانات النشر: | American Chemical Society (ACS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, RNase P, Pharmaceutical Science, 02 engineering and technology, Gene delivery, Transfection, 03 medical and health sciences, Ribonucleases, Plasmid dna, Drug Discovery, Polyamines, Humans, RNA, Messenger, chemistry.chemical_classification, Drug Carriers, Messenger RNA, Nuclease, biology, Chemistry, Biomolecule, DNA, Genetic Therapy, 021001 nanoscience & nanotechnology, Polyelectrolytes, 030104 developmental biology, Biochemistry, Nucleic acid, biology.protein, Helianthus, Molecular Medicine, 0210 nano-technology, HeLa Cells, Plasmids |
| الوصف: | Messenger RNA (mRNA) is a biomolecule with a wide range of promising clinical applications. However, the unstable nature of mRNA and its susceptibility to degradation by ribonucleases (RNases) necessitate the use of specialized formulations for delivery. Polycations are an emerging class of synthetic carriers capable of packaging nucleic acids, and may serve as suitable RNase-resistant formulations for mRNA administration. Here, we explore the application of VIPER and sunflower polycations, two polycations previously synthesized by our group, for the delivery of mRNA in comparison to branched poly(ethylenimine); all three polycations have been shown to efficiently deliver plasmid DNA (pDNA) to cultured cells. Despite successful mRNA condensation and packaging, transfection studies reveal that these three polycations can only efficiently deliver mRNA under serum-free conditions, while pDNA delivery is achieved even in the presence of serum. RNase resistance studies confirm that nuclease degradation of mRNA cargo remains a significant barrier to mRNA delivery using these polycations. These results emphasize the need for additional strategies for nuclease protection of mRNA cargo beyond electrostatic complexation with polycation. |
| تدمد: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.8b00134 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2d4f6d3f1d229f8bab3afd3a35dcfa8 https://doi.org/10.1021/acs.molpharmaceut.8b00134 |
| رقم الانضمام: | edsair.doi.dedup.....a2d4f6d3f1d229f8bab3afd3a35dcfa8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15438392 15438384 |
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| DOI: | 10.1021/acs.molpharmaceut.8b00134 |