Advancing cell therapies with lipid nanoparticles

Cell therapy has emerged as one of the most transformative frontiers in modern medicine, offering new ways to treat diseases by reprogramming living cells to enhance or restore their function. Whether sourced from a patient (autologous) or a donor (allogenic), cells can be isolated, modified, expanded, and reintroduced into the body to precisely target disease. One of the promising technologies driving these advancements, encouraging us to rethink cell therapy and reshape this field, is the lipid nanoparticle (LNP). Validated in mRNA vaccine platforms, LNPs are now being reimagined as precision delivery systems.

LNPs play an increasingly important role in cell therapy research and development, offering a flexible, non-viral gene-delivery platform for modulating gene expression or achieving precise gene editing. They function as transient reprogramming agents that support the controlled expression of target genes or molecular tools, such as chimeric antigen receptors (CAR) or CRISPR-Cas9 components. This transient approach offers a unique advantage by allowing the evaluation of different constructs and process parameters while maintaining cellular integrity and genomic stability.

As the field of RNA-LNP technology matures, its application in cell therapy manufacturing is gaining momentum. Researchers are leveraging LNPs to engineer immune and stem cells ex vivo, optimize genetic payload design, and establish scalable, reproducible delivery processes. Combined with advanced formulation, process analytics, and automation, LNP-based delivery is poised to become a cornerstone of next-generation cell therapy development.

What are LNPs, and how do they work

Lipid nanoparticles are nanoscale delivery systems made of ionizable lipids, phospholipids, cholesterol, and PEG-lipids that encapsulate and protect fragile mRNA molecules from degradation. These components form a protective shell around the mRNA payload, allowing it to safely enter target cells through endocytosis. Once inside, pH-triggered ionization facilitates endosomal escape and cytoplasmic release of the mRNA, enabling protein translation. In cell therapy applications, this means LNP-mRNA can transiently express therapeutic proteins such as chimeric antigen receptors (CAR) or genome editing enzymes without altering the host genome. This transient expression improves safety and control, particularly when reprogramming patient-derived immune or stem cells.

Role of lipid nanoparticles in modern cell therapy

Whether you’re developing CAR T or editing hematopoietic stem cells (HSC), LNPs offer a gentler, more consistent path from formulation to transfection to scale-up—an effective alternative to electroporation. Unlike viral vectors, which rely on cell-based production systems that can introduce additional complexity, LNP-mRNA platforms offer a non-viral, transient, and customizable approach to delivering genetic instructions.

Applications include:

• CAR T cell generation – delivering mRNA encoding CAR constructs for efficient, transient receptor expression
• Gene-editing – enabling CRISPR-Cas 9 mRNA and guide RNA co-delivery to precisely modify immune or stem cells.
• Cell reprogramming – using mRNA-lipid nanoparticles to express transcription factors that convert somatic cells into induced pluripotent stem cells (iPSCs)

This flexibility allows scientists to design safer and faster workflows while reducing regulatory complexity.

Explore how leading research groups use LNPs to advance CAR T and HSC therapies.

How is reprogramming cells with mRNA-LNP done

1. T cell isolation: The patient’s T cells are isolated.
2. mRNA encapsulation: mRNA encoding the CAR that targets disease-specific biomarkers is encapsulated into LNP.
3. mRNA delivery: The LNP mediates delivery of the mRNA into T cells ex vivo.
4. CAR expression: T cells translate the mRNA into CAR proteins, which are presented on the cell surface.
5. T cell expansion and infusion: The engineered CAR T Cells are expanded and infused back into the patient, where they mount an immune response to the target recognized by the CAR.

Fig 1. Autologous chimeric antigen receptor T cells engineering with non-viral gene delivery

Benefits of using LNPs in cell therapy development

The versatility of lipid nanoparticles lies in their ability to efficiently deliver therapeutic nucleic acids while maintaining the health and functionality of target cells. Their composition and tunable properties enable a fine balance between delivery efficiency, safety, and manufacturability, making them an ideal fit for cell therapy manufacturing and gene-modified cell development.

• Transient and non-integrative gene delivery 

  LNP-mediated delivery enables temporary expression of mRNA or gene-editing tools without altering the host genome. This transient profile allows researchers to evaluate multiple targets or constructs while minimizing risks of insertional mutagenesis and preserving cellular function.
  
  

• Enhanced transfection efficiency and cell viability 

  LNPs can be tailored for high encapsulation efficiency and effective cytoplasmic release, leading to robust protein expression. Their gentle mechanism of membrane fusion helps maintain cell viability and phenotype integrity, supporting consistent manufacturing outcomes.
  
  

• Compatibility with diverse RNA payloads 

  LNP formulations can be tailored for specific cell types, enabling broader applications across CAR T, NK cells, and gene-edited therapies. The modularity of LNP formulation simplifies optimization for specific payload characteristics.
  
  

• Scalable, controlled manufacturing and simplified production 

  LNPs do not require complex cell culture or viral packaging, making production faster and more scalable. From benchtop optimization to large-scale production, LNP manufacturing can be scaled using nanoparticle formulation systems such as the NanoAssemblr platforms. These systems allow precise control over particle size, composition, and reproducibility.
  
  

• Streamlined process integration 

  LNP-based delivery fits naturally into established cell therapy workflows. It can be applied following T-cell isolation or stem cell selection, integrated with expansion protocols, and adapted for GMP environments.
  
  

• Broad potential beyond CAR T 

  While CAR T cell engineering is a prominent example, LNP-mediated RNA delivery holds promise for other advanced modalities, including TCR therapies, NK cell reprogramming, and induced pluripotent stem cell (iPSC) modification. Its transient nature allows exploration of novel targets and cell phenotypes without the permanent genetic alterations associated with other delivery systems.

How LNPs enhance delivery and efficacy in cell therapies

Delivering mRNA efficiently and safely to immune cells is at the core of successful cell therapy development. Lipid nanoparticles play a key role by enabling non-viral delivery of genetic material to precisely reprogram cells ex vivo. In the cell therapy workflow, each stage, from isolation and activation of T cells to mRNA-LNP transfection, expansion, and harvest, relies on optimized systems that ensure consistency, viability, and scalability.

Cytiva applications and services for mRNA-LNP in cell therapy

Cytiva supports this process through a complete solution that connects upstream cell processing with LNP formulation and scalable manufacturing. It begins with cell isolation and preparation, where researchers separate and activate immune cells with Cytiva’s Sefia Select™ system, which helps maintain cell phenotype and purity, while reducing manual variability and minimizing contamination risks.

Next, mRNA encoding the therapeutic construct is encapsulated into LNPs. At the heart of efficient RNA delivery is formulation technology, a domain where Cytiva provides enabling tools that support both research and scale-up. Cytiva’s GenVoy-ILM delivery platform features a T cell Kit for mRNA, for the precise delivery of mRNA or CRISPR Cas9 mRNA with gRNA into human primary T cells, and the CD34+ HSC LNP kit LNP reagent mix optimized for the delivery of mRNA or Cas9 mRNA/sgRNA into CD34+ HSCs. These reagent kits are optimized, offering higher efficiency and good cell viability, a crucial factor in maintaining the yield of modified cells.

For scalable manufacturing, the NanoAssemblr™ Ignite platform, powered by NxGen™ mixing technology, allows reproducible production of RNA-LNP reagents from lab-scale testing to GMP-relevant batches. This platform continuity ensures smooth translation from discovery to clinical manufacturing.

Watch to learn how LNPs and Cytiva’s LNP-based workflow enhance cell viability, workflow efficiency, and reproducibility, advancing modern gene and cell therapy research.

Once the LNPs are ready, they step into the cell therapy process to deliver their cargo—gently and effectively. With Cytiva’s Xuri™ cell expansion system W25, you can maintain optimal conditions for transfection to support efficient and gentle gene transfer in a controlled, sterile environment. Following transfection, cells are expanded under controlled conditions while maintaining quality to achieve the desired therapeutic dose. The Cytiva platform offers precisely controlled conditions to ensure high cell yields, consistent product quality, and reduced operator intervention. The modified cells are then harvested and formulated using the Sefia Select™ system, preserving viability and phenotype for infusion, completing a workflow that is flexible, reproducible, and fully scalable. Together, Cytiva’s integrated suite of solutions enables a consistent and efficient workflow that advances LNP-enabled cell therapy manufacturing.

Recent advances in LNP technology for cell therapy applications

Research on LNP-based delivery continues to evolve, particularly in pairing LNPs with gene-editing systems such as CRISPR/Cas9. Studies have demonstrated successful co-encapsulation of Cas9 mRNA and guide RNAs in LNP for in vivo delivery and targeted editing (1, 2). Advances in lipid chemistry are also producing next-generation LNPs with improved biodegradability and cell-specific targeting, essential features for expanding use into cell therapy reprogramming and gene-modified immune cells (3).

Future Outlook

As cell and gene therapy development accelerates, LNP-mRNA systems will play a crucial role in enabling safer, faster, and more flexible engineering of therapeutic cells. Their non-viral, scalable, and transient characteristics align with the industry’s push towards manufacturing agility and clinical adaptability.

Combined with Cytiva’s integrated portfolio, this approach helps researchers move rapidly from concept to clinical applications in cell therapy manufacturing.

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