Diabetes mellitus is a mounting concern in the United States, as are the mortality and morbidity that result from its complications. Of particular concern, diabetes patients frequently suffer from impaired wound healing and resultant nonhealing diabetic foot ulcers. These ulcers overproduce tumor necrosis factor α (TNFα), which reduces wound bed cell migration and proliferation while encouraging apoptosis. Herein, we describe the use of siRNA-loaded lipid nanoparticles (LNPs) as a potential wound treatment to combat an overzealous immune response and facilitate wound closure. LNPs were formulated with an ionizable, degradable lipidoid and siRNA specific for TNFα. Topical application of nanoparticles reduced TNFα mRNA expression in the wound by 40-55% in diabetic and nondiabetic mice. In diabetic mice, this TNFα knockdown accelerated wound healing compared to untreated controls. Together, these results serve as proof-of-concept that RNA interference therapy using LNPs can reduce the severity and duration of chronic diabetic wounds.

Lipid nanoparticles silence tumor necrosis factor α to improve wound healing in diabetic mice

Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery

With the rapid development of gene therapy technology and the outbreak of coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) therapeutics have attracted more and more attention, and the COVID-19 mRNA vaccine has been approved by the Food and Drug Administration (FDA) for emergency authorization. To improve the delivery efficiency of mRNA in vitro and in vivo, researchers have developed a variety of mRNA carriers and explored different administration routes. This review will systematically introduce the types of mRNA vectors, routes of administration, storage methods, safety of mRNA therapeutics, and the type of diseases that mRNA drugs are applied for. Finally, some suggestions are supplied on the development direction of mRNA therapeutic agents in the future.

/pdf/applications-and-challenges-of-biomaterial-mediated-mrna-20moxxbd.pdf

Applications and challenges of biomaterial mediated mRNA delivery

Described are compositions and methods for inhibition of Hepatitis B virus gene expression RNA interference (RNAi) agents for inhibiting the expression of Hepatitis B virus gene are described The HBV RNAi agents disclosed herein may be targeted to cells, such as hepatocytes, for example, by using conjugated targeting ligands Pharmaceutical compositions comprising one or more HBV RNAi agents optionally with one or more additional therapeutics are also described Delivery of the described HBV RNAi agents to infected liver in vivo provides for inhibition of HBV gene expression and treatment of diseases and conditions associated with HBV infection

RNAi AGENTS FOR HEPATITIS B VIRUS INFECTION

This invention relates to compounds, compositions, and methods useful for reducing Glycolate Oxidase (HAO1) target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Methods and compositions for the specific inhibition of glycolate oxidase (HAO1) by double-stranded RNA

The invention relates to RNAi agents, e.g. double-stranded RNAi agents, targeting the HAO1 gene, and methods of using such RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1. Described herein are double-stranded RNAi agents which inhibit the expression of a HA01 gene in a cell, such as a cell within a subject, e.g., a mammal, such as a human having a HAO1 associated disorder, and uses of such double-stranded RNAi agents. In certain aspects of the invention, substantially all of the nucleotides of an iRNA of the invention are modified.

Compositions and methods for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression

Erratum: Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates (Proceedings of the National Academy of Sciences of the United States of America (2014) 111:11 (3955-3960) DOI:10.1073/pnas.1322937111)

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Compositions and methods for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression

Erratum: Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates (Proceedings of the National Academy of Sciences of the United States of America (2014) 111:11 (3955-3960) DOI:10.1073/pnas.1322937111)