// Aug 2026
Can Lipid Nanoparticles (LNPs) Replace Electroporation for T-Cell Engineering?
Optimized lipid nanoparticles can outperform electroporation in applications where cell health, durable expression, DNA delivery, and large gene insertion matter. That may not hold true in every T-cell engineering workflow today.
LNPs Offer a Non-Viral Alternative to Electroporation
Electroporation has long been a standard non-viral method for delivering genetic payloads into primary T cells. It is widely used because it is flexible and familiar, but it can also introduce cell stress, reduce viability, and limit performance with challenging payloads such as large DNA cargos.
At ElevateBio, we are developing lipid nanoparticle platforms designed to support efficient RNA and DNA delivery into primary human T cells. The goal is not simply to replace one delivery method with another. The goal is to expand what non-viral T-cell engineering can achieve when delivery efficiency, cell health, and payload flexibility are all prioritized.
LNPs Can Improve mRNA Delivery and CAR Expression
Efficient mRNA delivery is a core requirement for many T-cell engineering workflows. In primary human T cells, ElevateBio LNPs delivered eGFP mRNA more efficiently than a commercial T-cell transfection reagent while maintaining strong cell viability.
The same delivery advantage appeared in CAR mRNA engineering. When CD19 CAR mRNA was delivered by LNP, CAR expression remained more durable over time than with electroporation (see data in a technical poster of this work). Our proprietary LNPs achieved approximately 99% CAR-positive T cells on Day 2 and approximately 60% on Day 4, supporting the potential for LNPs to improve transient mRNA-based engineering workflows.
LNPs Can Support Functional Genome Editing
T-cell engineering requires more than expression. Delivery systems must also support functional genome editing when editors, guide RNAs, or other gene-editing components are introduced into cells.
ElevateBio RNA LNPs delivered nuclease and guide RNA payloads for TRAC knockout in primary human T cells. In these studies, LNP delivery supported potent TRAC knockout, with editing efficiency greater than 85%. That result shows that optimized LNPs can support functional editing performance, not only transient transgene expression.
DNA Delivery Is Where LNPs May Create the Greatest Advantage
Large DNA delivery remains one of the hardest problems in T-cell engineering. Electroporation can deliver DNA, but large cargos often reduce efficiency and increase stress on primary cells.
Our LNP platform, optimized for plasmid delivery into primary human T cells, delivered eGFP nanoplasmid DNA and achieved greater than 90% GFP-positive T cells.
The advantage became most apparent in large gene insertion. In an LSR-mediated CAR insertion workflow, RNA LNPs delivered LSR mRNA while DNA LNPs delivered the CAR donor DNA payload. The LNP-based system achieved up to approximately 88% CD19-CAR-positive T cells, compared with less than 20% insertion efficiency using electroporation.
LNPs Expand the Design Space for T-Cell Engineering
Electroporation remains an important tool, but optimized LNP systems can offer meaningful advantages in workflows that require efficient delivery, strong cell health, and flexible RNA and DNA payload handling.
LNPs are not just an alternative transfection method. For next-generation T-cell engineering, especially workflows involving large DNA insertion, LNPs may expand the range of non-viral engineering strategies available to developers.
Xiuying Li, Ph.D., Senior Scientist, Technology Development
Xiuying Li is a Senior Scientist specializing in lipid nanoparticle (LNP) delivery systems for gene editing and mRNA therapeutics, with expertise in nanomedicine, biomaterials, and nucleic acid delivery.
At ElevateBio, she has been central to developing proprietary LNP platforms for ex vivo and in vivo delivery of gene editing machinery and nucleic acid therapeutics, spanning formulation development, targeted delivery, process development, and translational research.
Previously at Immorna Therapeutics, she focused on the discovery, optimization, and scale-up of LNP systems for mRNA vaccines and therapeutics targeting infectious diseases and oncology diseases.
Xiuying holds a Ph.D. in Pharmaceutical Sciences and has built her career at the intersection of drug delivery, gene editing, and translational medicine. Motivated by the impact of rare genetic disease within her family, she is passionate about developing therapies that transform patients' lives.
