Genetically modified T cells (CAR T/TCR T) are a transformative oncology breakthrough, but viral vectors limit scalability and expansion beyond cancer. mRNA provides a transient, non-integrative alternative, eliminating insertional mutagenesis with dose-controllable activity and enabling in situ T cell programming.
Creative Biolabs' Custom mRNA based T Cell Reprogramming Service accelerates lead validation via optimized IVT mRNA and efficient non-viral delivery. It offers end-to-end, research-backed solutions for ex vivo/in vivo applications, enabling safer, targeted T-cell therapeutics from design to clinic.
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T cell reprogramming involves introducing genetic information that codes for a new receptor—typically a Chimeric Antigen Receptor (CAR) or an affinity-optimized T Cell Receptor (TCR)—to redirect the T cell's specificity toward a disease-associated antigen. Using mRNA for this process means:
Fig.1 T cells were reprogrammed in situ using IVT mRNA carried by polymer nanoparticles to express disease-specific Cars or TCRS.1,3
Our comprehensive workflow is designed for transparency and precision, ensuring every project phase is optimized for success.
Design IVT mRNA template with optimized UTRs, codon usage, and chemical modifications (e.g., CleanCap, m1ψ). Outcome: Optimized plasmid/template.
High-yield IVT plus advanced purification to remove immunogenic impurities. Outcome: High-purity modified mRNA.
Optimize non-viral delivery (e.g., Electroporation) for >80% viability and >90% transfection efficiency. Outcome: Optimized cell modification SOP.
In vitro testing against target cells to measure expression kinetics, cytokine production, and cytotoxicity. Outcome: Functional validation data.
Formulate mRNA into customized LNPs/polymer nanocarriers for systemic T-cell targeting. Outcome: Injectable nanocarrier formulation.
8–14 weeks, depending on CAR/TCR sequence complexity, mRNA production scale, and nanocarrier formulation requirements.
As a biology expert, you demand precision and innovation. Creative Biolabs' Custom mRNA based T Cell Reprogramming Service provides the scalable, non-viral solution your cutting-edge research requires, guaranteeing high performance and customization at every step.
Customizable mRNA Chemistry & Engineering
Tailor IVT mRNA constructs with codon optimization, 5'/3' UTR selection, and advanced capping analogs (e.g., CleanCap) to boost translational output and longevity across T-cell subtypes.
Precision Transient Control
Custom-design CAR/TCR expression kinetics (hours to days) to achieve desired therapeutic windows, minimizing toxicity and controlling immune responses in sensitive applications.
Dual Delivery Expertise
Master high-efficiency ex vivo electroporation (for clinical manufacturing) and custom LNP/polymeric carrier formulation (for systemic in vivo T-cell targeting).
Immunogenicity Minimization
Use modified nucleotides (e.g., N1-methylpseudouridine) and rigorous dsRNA removal to reduce innate immune activation, maximizing in vivo therapeutic efficacy.
Seamless Scale-Up & GMP Readiness
Provide QC-verified mRNA scalable from milligram (discovery) to multi-gram (preclinical/early-phase GMP) quantities.
Comprehensive Quality-by-Design (QbD)
Implement established quality systems across workflows, with batch-wise capping efficiency and integrity verification for consistent T-cell modification.
To enhance the safety and controllability of CAR-T cell therapy, some studies designed relevant IVT-mRNA, detected its basic structure and functional characteristics, and then delivered it into AML patients via LNP. The patients' T cells were transfected, and the CAR expression and cytotoxicity were detected. After mRNA transfection of T cells, the time when CAR was detected was as long as 4 days. Compared with untransfected T cells, mRNA-CAR-T had stronger cytotoxicity to target cells.
Fig.2 IVT-mRNA enhances the generation and efficacy of CAR-T cells derived from T cells of AML patients.2,3
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Viral vectors lead to permanent, stable expression, which is effective for aggressive cancer but carries risks of long-term toxicity and off-target effects. Our mRNA service provides transient expression (lasting days), which is crucial for therapeutic control and safety in treating non-oncology conditions like autoimmune disease and fibrosis. We optimize the mRNA chemistry (using superior caps and modifications) to maximize this temporary expression window.
We are fully equipped for both. While we optimize high-efficiency ex vivo electroporation protocols (>90% transfection) for traditional manufacturing, our expertise extends to custom nanocarrier formulation (LNP and polymer). This enables you to pursue cutting-edge in vivo strategies that aim to intravenously deliver the CAR-mRNA to circulating T cells, achieving a systemic, injectable cell therapy approach.
Immunogenicity is a critical concern, especially for in vivo applications. We employ two key strategies: first, using advanced capping analogs (e.g., CleanCap) and modified nucleotides (e.g., N1-methylpseudouridine) to trick the T cell's immune sensors; and second, performing rigorous purification post-IVT to remove residual double-stranded RNA (dsRNA) impurities, which are a major trigger for the innate immune response.
Our optimized electroporation protocols consistently yield T-cell viability exceeding 80% and transfection efficiency greater than 90% in primary human T cells. We provide detailed SOPs and validation reports to ensure this high efficiency is reproducible, translating directly into a reliable and high-yield therapeutic product.
Creative Biolabs offers the industry's most robust and scientifically validated platform for the Custom mRNA based T Cell Reprogramming Service. By mastering transient expression, advanced mRNA chemistry, and non-viral delivery, we eliminate the roadblocks of traditional viral manufacturing and unlock the vast therapeutic potential of in vivo cell engineering. From target validation to GMP-ready protocols, we are your essential partner in the new era of immunotherapy.
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