mRNA-Driven T Cell Reprogramming Service

T lymphocytes (T cells) are central orchestrators of adaptive immunity, making them high-value targets for reprogramming in biomedical research. Creative Biolabs leverages mRNA-based reprogramming technology to transiently engineer T cell specificity, function, and persistence—without genomic integration or permanent genetic alteration. Our services empower researchers investigating cancer immunology, autoimmune pathogenesis, and regenerative medicine with a safe, scalable, and precise platform.

Technology Overview

mRNA-mediated reprogramming represents a paradigm shift in adoptive cell engineering. Unlike viral vectors or CRISPR-Cas9 genome editing (which can lead to insertional mutagenesis or off-target effects), mRNA carries transient genetic instructions to T cells. These instructions program high levels of chimeric antigen receptors (CARs), T cell receptors (TCRs), or immunomodulatory factors for 48-72 hours (enough to study acute functional effects but not off-target toxicity). Creative Biolabs synthesizes research-grade mRNA featuring:

• 5' Cap1 structure and optimized poly-A tails for enhanced translational efficiency
• Nucleotide modifications to reduce innate immune recognition
• Optional fluorescent labeling (Cy3/Cy5) for cell tracking

Core Research Services

mRNA-Driven T Cell Reprogramming

Creative Biolabs offers a comprehensive suite of mRNA-driven T cell reprogramming services tailored for cutting-edge in vitro and in vivo research applications. Our platform enables transient, precise, and safe modification of T cells to investigate fundamental immunology and therapeutic concepts. Key services include:

Chimeric Antigen Receptor (CAR) & T Cell Receptor (TCR) Engineering:

• Purpose: Introduce novel antigen specificity to T cells for targeted immune recognition studies.
• Focus: Transient expression to study acute functional outcomes and avoid long-term phenotypic drift.

Immunomodulatory Factor Expression:

• Purpose: Deliver mRNA encoding cytokines, chemokines, co-stimulatory molecules, or soluble factors to modulate T cell function and microenvironment interactions.
• Focus: Precisely timed and transient delivery to mimic physiological immune signaling dynamics or test specific hypotheses.

T Cell Phenotype Reprogramming & Polarization:

• Purpose: Drive T cells towards specific functional states (e.g., effector, memory, regulatory - Treg, Th1, Th2, Th17).
• Focus: Transient expression of key transcription factors or signaling molecules to induce and analyze phenotypic shifts.

Combinatorial & Sequential Reprogramming:

• Purpose: Co-deliver or sequentially deliver multiple mRNA payloads to investigate synergistic effects and complex cell behaviors.
• Focus: Enabling sophisticated experimental designs to dissect complex immunological pathways without permanent genetic alteration.

Targeted In Vivo T Cell Reprogramming:

• Purpose: Directly deliver mRNA payloads to T cells within a living organism using our advanced LNP platform.
• Focus: Transient, cell-type specific modification for real-time analysis of immune dynamics in situ.

Service Advantages

• Transience & Safety: Ideal for mechanistic studies requiring reversible modifications and minimizing genotoxic risk.
• Flexibility & Speed: Rapid design and synthesis of mRNA payloads for testing diverse hypotheses.
• Precision: Controlled expression levels and kinetics for more physiologically relevant modeling.
• Species Agnostic: Applicable across human, mouse, and NHP primary T cells and models.
• Customization: Tailored payload design to meet specific research objectives.

Related mRNA Services

Case Examples & Emerging Directions

Fig.1 mRNA-Driven T Cell Reprogramming.

The Future: Multi-Antigen Targeting & Logic Gates

We are developing:

• Sequential mRNA dosing to program "AND-gate" CAR-T activity
• mRNA-encoded synthetic receptors that induce secondary cytokine expression upon antigen engagement
• In vivo generated CAAR-T cells for B cell depletion in autoimmune research

Technology Differentiation & Innovations

Creative Biolabs integrates the latest advances to overcome historical T cell engineering bottlenecks:

• Epigenetic Reprogramming Enhancements

Co-delivery of mRNA encoding rejuvenating transcription factors counteracts T cell exhaustion and enhances stemness—critical for sustaining anti-tumor activity in repetitive challenge models.

• Advanced LNP Delivery

Our optimized ionizable lipids improve T cell-targeted transfection while reducing hepatotoxicity.

• Safety by Design

mRNA's transient activity eliminates risks of genomic integration, making it ideal for:

• Studies requiring reversible immune modulation
• Humanized models with stringent safety requirements
• High-throughput screens testing multiple receptor designs

Comparison of T Cell Engineering Approaches for Research Use

Integrated LNP-mRNA Platform for In Vivo T Cell Engineering

Creative Biolabs pioneers a synergistic research platform merging targeted LNP delivery with mRNA reprogramming to enable direct in vivo T cell modification. This integrated approach bypasses ex vivo manipulation artifacts, allowing real-time study of immune cell dynamics in physiological contexts.

Core Innovations

• Cell-Specific Targeting: LNPs functionalized with T-homing ligands achieve lymphoid tissue-selective delivery, minimizing off-target transfection.
• Immunologically Silent Expression: Engineered mRNA with stealth UTRs prevents unintended immune activation during transfection.
• Modular Payload Capacity: Single-vector co-encapsulation of multiplexed genetic payloads (e.g., CAR mRNA + immunomodulators) supports combinatorial studies.

Partner with Creative Biolabs

Creative Biolabs delivers end-to-end mRNA-driven T cell reprogramming services that merge targeted nanoparticle delivery with immune-specific genetic design. Our platform empowers researchers to dissect fundamental immunology mechanisms and therapeutic concepts through customizable T cell modifications—without viral vectors or ex vivo manufacturing constraints. As leaders in immunology and cell engineering, we offer:

• Species-specific designs: Human, mouse, non-human primate models
• Custom immunomodulatory construction: From CARs/TCRs to checkpoint modulators
• Complete in vitro/in vivo validation packages
• Cell-State Preservation: Low-immunostimulatory LNPs avoid unintended T cell activation, maintaining native phenotypes during reprogramming

Partner with our immunology and nanomedicine specialists to deploy this technology in your research. Specify your reprogramming goals (e.g., target antigen, disease model, payload type) for a customized project roadmap. Contact us to request validation data, case studies, or feasibility assessments.

FAQs

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Reference

1. Zhang, Zihan, et al. "Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in-vivo CAR-T therapy for inflamm-aging." bioRxiv (2024): 2024-11. Distributed under Open Access license CC-BY-NC-ND 4.0, without modification. https://doi.org/10.1101/2024.11.21.624667