Lipid encapsulated messenger RNA (LNP mRNA) has garnered a significant amount of interest from the pharmaceutical industry and general public alike. This attention has been catalyzed by the clinical success of LNP mRNA for SARS-CoV-2 vaccination as well as future promises that might be fulfilled by the biotechnology pipeline, such as the in vivo delivery of a CRISPR/Cas9 complex that can edit patient cells to reduce levels of low-density lipoprotein. LNP mRNAs are comprised of various chemically diverse molecules brought together in a sophisticated intermolecular complex. This can make it challenging to achieve thorough analytical characterization. Nevertheless, liquid chromatography is becoming an increasingly relied upon technique for LNP mRNA analyses. Although there have been significant advances in all types of LNP mRNA analyses, this review focuses on recent developments and the possibilities of applying anion exchange (AEX) and ion pairing reversed phase (IP-RP) liquid chromatography for intact mRNAs as well as techniques for oligo mapping analysis, 5' endcap testing and lipid compositional assays.
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http://dx.doi.org/10.1016/j.jpba.2022.115174 | DOI Listing |
J Transl Med
January 2025
Hepatology Laboratory, Solid Tumors Program, CIMA, CCUN, University of Navarra, Pamplona, Spain.
Background: Acute pancreatitis (AP) presents a significant clinical challenge with limited therapeutic options. The complex etiology and pathophysiology of AP emphasize the need for innovative treatments. This study explores mRNA-based therapies delivering fibroblast growth factor 21 (FGF21) and apolipoprotein A1 (APOA1), alone and in combination, for treating experimental AP.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
March 2025
Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA.
Lipid nanoparticles (LNPs) are often liver tropic, presenting challenges for LNP-delivered mRNA therapeutics intended for other tissues, as off-target expression in the liver may increase side effects and modulate immune responses. To avoid off-target expression in the liver, miR-122 binding sites have been used by others in viral and non-viral therapeutics. Here, we use a luciferase reporter system to compare different copy numbers and insertion locations of miR-122 binding sequences to restrict liver expression.
View Article and Find Full Text PDFMater Today Bio
February 2025
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, 226000, China.
A next-generation STING agonist MSA-2 is a promising tumor immunotherapy strategy. However, the methods for improving the anti-tumor efficacy of MSA-2 are a lot of effort. We have demonstrated antitumor effect of platinum-modified MSA-2 (MSA-2-Pt) was better than MSA-2.
View Article and Find Full Text PDFMol Ther
January 2025
Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address:
Exemplified by successful use in COVID-19 vaccination, delivery of modified mRNA encapsulated in lipid nanoparticles provides a framework for treating various genetic and acquired disorders. However, lipid nanoparticles that can deliver mRNA into specific lung cell types have not yet been established. Here, we sought whether poly(®-amino ester)s (PBAE) or PEGylated PBAE (PBAE-PEG) in combination with 4A3-SC8/DOPE/cholesterol/DOTAP lipid nanoparticles (LNP) could deliver mRNA into different types of lung cells in vivo.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Lipid nanoparticles (LNPs) are the preeminent non-viral drug delivery vehicle for mRNA-based therapies. Immense effort has been placed on optimizing the ionizable lipid (IL) structure, which contains an amine core conjugated to lipid tails, as small molecular adjustments can result in substantial changes in the overall efficacy of the resulting LNPs. However, despite some advancements, a major barrier for LNP delivery is endosomal escape.
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