Journal of biotechnologyMay 13, 2026

Higher mRNA delivery per RNA amount by concentrating cells

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated May 14, 2026

Abstract

Achieving approximately 55% GFP+ T cells was possible while using about 40-fold less mRNA per million concentrated cells.

Concentrating human T and NK cells significantly enhances gene delivery efficiency compared to standard methods.
Using lipid nanoparticles for mRNA transfection can increase the number of GFP+ cells per ng of mRNA by up to 30-fold.
The approach may reduce costs associated with T-cell therapy manufacturing.
Transient transfection with this method could allow for repeated dosing, potentially improving safety and effectiveness.

Simplified

The availability of T-cell therapies is limited in part due to their complex and costly biomanufacturing. Genetic engineering of T cells, such as to express chimeric antigen receptor (CAR), is commonly achieved using viral vectors, that are costly to produce and add to safety concerns. Non-viral alternatives have advantages, but a major barrier is their far lower efficiency of gene delivery. This has motivated the development of new strategies to increase nonviral gene delivery efficiencies, including using lipid nanoparticles (LNPs). We investigated the transfection of human T and NK cells with three formulations of green fluorescent protein (GFP) mRNA-LNPs and found that concentrating cells greatly increased transfection per ng mRNA, compared to conventional methods. We achieved ∼55% GFP+ T cells with both protocols, while using ∼40-fold less mRNA per million concentrated cells. This resulted in up to a 30-fold increase in the number of GFP+ cells per ng mRNA. The developed process should reduce manufacturing costs and would enable transient transfection with repeated dosing that could improve treatment safety and efficacy, making life-saving therapies available to more patients.

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Competing interests

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

Higher mRNA delivery per RNA amount by concentrating cells

Abstract

Full Text

Funding

Competing interests

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