Expert opinion on drug deliveryJan 11, 2025

Development plan for mRNA delivery particles aimed at genome editing treatments in the liver

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 6, 2026

Abstract

mRNA therapeutics are now utilized in various applications, including vaccine development and therapeutic genome editing.

Lipid nanoparticles (LNPs) are essential for delivering mRNA into cells, enabling the translation of disease-modifying proteins.
The design of LNPs involves a cycle of design, making, testing, and analysis to optimize their effectiveness.
Ionizable lipids are a key component in the development of LNPs for therapeutic genome editing.
Collaborations between academia and industry have improved understanding of critical processes like endosomal escape and LNP structure.
Insights gained from these collaborations could inform the development of next-generation delivery systems for nucleic acid therapies.

Simplified

INTRODUCTION: mRNA therapeutics were a niche area in drug development before COVID vaccines. They are now used in vaccine development, for non-viral therapeutic genome editing,chimeric antigen receptor T (CAR T) cell therapies and protein replacement. mRNA is large, charged, and easily degraded by nucleases. It cannot get into cells, escape the endosome, and be translated to a disease-modifying protein without a delivery system such as lipid nanoparticles (LNPs). in vivo

AREAS COVERED: This article covers how to design, select, and develop an LNP for therapeutic genome editing in the liver. The roadmap is divided into selecting the right LNP for discovery via a design, make, test, and analyze cycle (DMTA). The design elements are focused on ionizable lipids in a 4-component LNP, and insights are provided for how to set anandtesting strategy. The second section focuses on transforming the LNP into a clinical drug product and covers formulation, analytical development, and process optimization, with brief notes on supply and regulator strategies. in vitro in vivo

EXPERT OPINION: The perspective discusses the impact that academic-industry collaborations can have on developing new medicines for therapeutic genome editing in the liver. From the cited collaborations an enhanced understanding of intracellular trafficking, notably endosomal escape, and the internal structure of LNPs were attained and are deemed key to designing effective and safe LNPs. The knowledge gained will also enable additional assays and structural activity relationships, which would lead to the design of the next-generation delivery systems for nucleic acid therapies.

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Development plan for mRNA delivery particles aimed at genome editing treatments in the liver

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