Lipid nanoparticle-encapsulated mRNA therapy corrects serum total bilirubin level in Crigler-Najjar syndrome mouse model

Greig, Jenny A.; Chorazeczewski, Joanna K.; Chowdhary, Vivek; Smith, Melanie K.; Jennis, Matthew; Tarrant, James C.; Buza, Elizabeth L.; Coughlan, Kimberly A.; Martini, Paolo G.V.; Wilson, James M.

doi:10.1016/j.omtm.2023.02.007

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…Forty-two days postadministration, the serum total bilirubin levels in adult UGTIAI knockout mice returned to normal. 158 Cholestasis. Wei et al developed hABCB4 mRNA-loaded LNPs for the treatment of progressive familial intrahepatic cholestasis (PFIC3).…”

Section: Treatments For Hepatic Disordersmentioning

confidence: 99%

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Lipid nanoparticles as the drug carrier for targeted therapy of hepatic disorders

Chu,

Wang,

Kong

et al. 2024

J. Mater. Chem. B

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Section: Treatments For Hepatic Disordersmentioning

confidence: 99%

“…Forty-two days postadministration, the serum total bilirubin levels in adult UGTIAI knockout mice returned to normal. 158…”

Section: Hepatic-targeted Delivery and Therapymentioning

confidence: 99%

Lipid nanoparticles as the drug carrier for targeted therapy of hepatic disorders

Chu,

Wang,

Kong

et al. 2024

J. Mater. Chem. B

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“…The recent COVID-19 pandemic triggered an unprecedented revolution in biomedicine that resulted in an emergence of messenger RNA (mRNA) as a modality with immense therapeutic potential demonstrated primarily by mRNA-1273 [1] and BNT162b2 [2] mRNA vaccines against SARS-CoV-2. Their potential clinical utility has furthermore been demonstrated in a wide number of recent studies in cancer [3][4][5], CRISPR-Cas9-based treatment [6], anaphylaxis [7], and rare diseases [8]. mRNA coding for antibody fragments has been shown as a potential replacement for monoclonal antibody-therapy [9].…”

Section: Introductionmentioning

confidence: 99%

Scalable multimodal weak anion exchange chromatographic purification for stable mRNA drug substance

Megušar,

Miklavčič,

Korenč

et al. 2023

Electrophoresis

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Messenger RNA (mRNA) has emerged as a modality with immense therapeutic potential. Recent innovations in production process of mRNA call for procedures to isolate pure mRNA drug substance (DS) with high yield, high capacity, scalability, and compatibility with GMP production systems. Novel RNA modalities, such as circular RNA (circRNA), have further driven the need for non‐affinity capture possibilities which are already widely used in the biopharmaceutical industry, for example, in monoclonal antibody processing. The principle that multimodal ion exchange/hydrogen bonding chromatography can be used to separate mRNA from in vitro transcription components has recently been demonstrated. Here, we apply and refine this approach to be suitable for scalable purification of multiple mRNA constructs with sufficient yields, purity, and stability, for use in mRNA production process. Binding capacity of the PrimaS‐modified monolithic chromatographic column for mRNA enabled up to 7 mg/mL product isolation in a single chromatographic run, with 98% recovery and room temperature stability of the eGFP mRNA demonstrated for up to 28 days. This approach is independent of construct size or the presence of polyadenylic acid tail and is applicable for capture of a wide variety of RNAs, including mRNA, self‐amplifying RNA, circRNA, and with optimization also smaller RNAs such as transfer RNA and others.

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Liver gene transfer for metabolite detoxification in inherited metabolic diseases

D'Alessio,

Boffa,

De Stefano

et al. 2024

FEBS Letters

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Inherited metabolic disorders (IMDs) are a growing group of genetic diseases caused by defects in enzymes that mediate cellular metabolism, often resulting in the accumulation of toxic substrates. The liver is a highly metabolically active organ that hosts several thousands of chemical reactions. As such, it is an organ frequently affected in IMDs. In this article, we review current approaches for liver‐directed gene‐based therapy aimed at metabolite detoxification in a variety of IMDs. Moreover, we discuss current unresolved challenges in gene‐based therapies for IMDs.

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Lipid nanoparticle-encapsulated mRNA therapy corrects serum total bilirubin level in Crigler-Najjar syndrome mouse model

Cited by 5 publications

References 36 publications

Lipid nanoparticles as the drug carrier for targeted therapy of hepatic disorders

Lipid nanoparticles as the drug carrier for targeted therapy of hepatic disorders

Scalable multimodal weak anion exchange chromatographic purification for stable mRNA drug substance

Liver gene transfer for metabolite detoxification in inherited metabolic diseases

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