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Custom mRNA based Cell Reprogramming Services

Introduction mRNA based Cell Reprogramming Workflow What We Can Offer FAQ

Introduction

Cellular reprogramming (e.g., iPSC generation) underpins regenerative medicine. Early integration of viral vectors carried oncogenic risks via genomic alteration. Creative Biolabs' Custom mRNA-based Cell Reprogramming Services offer non-integrating, footprint-free solutions using modified/saRNA, ensuring safety and efficiency.

The service accelerates clinical-grade cell product development, eliminating insertional mutagenesis risks. With precise, scalable technologies, it supports research-to-clinical transition, enabling high-quality cell lines for regenerative medicine and next-gen immunotherapy.

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Custom mRNA based Cell Reprogramming Services

Creative Biolabs offers specialized mRNA services tailored to diverse therapeutic applications, ensuring that your starting material is optimally converted or modified for its final clinical purpose.

T Cell Reprogramming by mRNA Dendritic Cell Reprogramming by mRNA
High-efficiency, non-viral delivery of synthetic mRNA for the transient or stable expression of chimeric antigen receptors (CARs) or other engineering factors in primary T cells. This allows for rapid, scalable production of next-generation CAR-T therapies while maintaining high cell viability and avoiding the permanent integration risks associated with viral delivery. Utilizing customized mRNA to load antigens or modulate the expression of transcription factors and cytokines within dendritic cells. This is a powerful tool for developing personalized cancer vaccines and optimizing the antigen-presenting function of the cells ex vivo or in vivo.
Natural Killer Cell Reprogramming by mRNA B Cell Reprogramming by mRNA
Specialized protocols for transfecting sensitive Natural Killer (NK) cells with synthetic mRNA encoding activating receptors (e.g., CCR7, CD16) or CARs. Our method ensures rapid transgene expression, high viability, and preserves the intrinsic cytotoxic function of NK cells for allogeneic immunotherapy. Leveraging mRNA to induce pluripotency in B cells or to modify their function. This often involves factor cocktails (e.g., Yamanaka factors OSKM) to dedifferentiate early-stage B cells, or supplementary factors to modify mature B cells for research into antibody production and immunological memory.
iPSC Reprogramming by mRNA
The core service for regenerative medicine. We deliver optimized cocktails of modified mRNA encoding transcription factors (OCT4, SOX2, KLF4, cMYC, etc.) into somatic cells. This guarantees the generation of high-quality, clinical-grade iPSC lines with superior efficiency and no genomic footprint, ready for differentiation into complex cell types like neurons or cardiomyocytes.

Workflow

The typical process is designed to be clear, iterative, and optimized for speed and quality control.

Required Starting Materials

  1. Source Cell Line Information: Detailed characterization of the patient or donor somatic cells (e.g., Fibroblasts, Peripheral Blood Mononuclear Cells (PBMCs), T cells, or B cells), including passage number and culture conditions.
  2. Reprogramming Factor Requirements (Optional): Specific factor cocktail requested (e.g., OSKM, or specialized immune cell factors like CCR7/CD16), including desired stoichiometry.
  3. Target Differentiation Marker: Final cell type goal (e.g., Cardiomyocytes, iPSC, or CAR-T cells) to inform downstream quality control.
Consultation & Design
Sequence Optimization

Initial Consultation and Design

Finalize reprogramming strategy (modified mRNA/saRNA choice) and optimal non-viral delivery system (e.g., LNP, electroporation) for client’s source cells.

Custom mRNA Synthesis and Modification

Synthesize high-quality capped/polyadenylated mRNA with proprietary nucleoside modifications (e.g., Pseudouridine, 5-Methylcytidine) to boost stability and silence innate immunity.

Chemical Modifications
Synthesis & Purification

Cell Reprogramming and Culture Optimization

Apply optimized daily/single-shot transfection, manage specialized media and low-oxygen culture conditions to maximize reprogramming efficiency and colony formation.

Colony Isolation and Expansion

Mechanically isolate high-quality, morphologically correct colonies; expand under feeder-free, defined conditions to generate a master cell bank.

Quality Control & Validation
Delivery & Support

Quality Control and Characterization

Conduct comprehensive analysis (karyotyping, pluripotency/marker flow cytometry, integration-free PCR).

Final Deliverables

  1. Certificate of Analysis (CoA): Detailed documentation of the final cell line’s quality control results, including sterility, cell viability, and marker expression data.
  2. Footprint-Free Status Report: Molecular data confirming the non-integration and rapid clearance of the mRNA vector.
  3. Expanded Cell Line: Cryopreserved vials of the fully characterized, reprogrammed cell line, ready for downstream differentiation or use.
Consultation & Design
Delivery & Support

Estimated Timeframe

The typical timeframe for iPSC generation and characterization using our service ranges from 8 to 14 weeks, depending on the complexity of the starting cell type and the scope of the required Quality Control assays.

What We Can Offer

Our Custom mRNA based Cell Reprogramming Services platform, provided by Creative Biolabs, delivers unparalleled control and quality in non-viral cell engineering:

Footprint-Free Technology Guarantee
Use non-integrating modified mRNA for cell lines (iPSCs, modified T/NK cells) to eliminate residual vector traces and insertional mutagenesis risk for clinical translation.

Nucleoside Modification Expertise
Custom synthesize and incorporate proprietary nucleoside analogs (e.g., Pseudouridine, 5-Methylcytidine) to enhance mRNA stability, translation efficiency, and reduce innate immune response.

Flexible Reprogramming Mode Selection
Offer tailored strategies: high-yield stabilized modified mRNA (daily dosing) or saRNA (single-shot reprogramming) to cut hands-on time and accelerate timelines.

Custom Cell Type and Factor Cocktails
Provide specialized protocols for diverse source cells (T/B/NK cells, Dendritic cells, Fibroblasts) with adjustable factor stoichiometry (e.g., OSKM ratios) for project-specific needs.

Optimized Non-Viral Delivery Solutions
Support selection and optimization of efficient, non-toxic delivery systems (custom LNP formulations, electroporation parameter fine-tuning) for specific cell types.

Scalability for Industrialization
Enable seamless small-to-large-scale production transition with standardized, cGMP-compatible materials/processes for late-stage development consistency.

Case Study

Some studies have used synthetic RNA to prepare iPS cells from PBMCs. Although the methods and frequencies of RNA transfection have been optimized for PBMCs. Approximately 14 days after the initial RNA transfection, iPS cell-like colonies of sufficient size emerged, and MDM4 mRNA significantly enhanced the efficiency of PBMCs reprogramming. iPS cell clones established using synthetic RNA from PBMCs exhibit normal colony morphology and karyotype, and their gene expression is similar to that of mature iPS cell lines. Immunostaining showed that PAX6, KRT12, and p63 were co-expressed and successfully differentiated into corneal epithelioid cells.

Generation of iPS cells from PBMCs using synthetic RNA. (OA Literature)Fig.1 IPSCs were generated from PBMC using mRNA synthesized in vitro.1

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Customer Reviews

  • Exceptional Safety & Efficiency "Using Creative Biolabs' Custom mRNA-based Cell Reprogramming Services in our research has significantly improved the speed and confidence of our lead identification phase. The confirmed footprint-free status eliminates a major bottleneck, and the high colony yield minimizes the need for high-throughput screening of poor-quality lines."

    — Dr. Alan Newman (8 weeks ago)

  • Superior Immune Cell Modification "Using Creative Biolabs' T Cell Reprogramming by mRNA in our research has significantly facilitated the non-viral engineering of CAR constructs. Compared to electroporated plasmids, the transient, high-level expression from the modified mRNA resulted in far higher T cell viability and maintained functional cytotoxicity, which is crucial for our in vivo models."

    — Prof. Claire Fox (4 months ago)

  • Reliable Scalability "Using Creative Biolabs' iPSC Reprogramming by mRNA in our research has significantly improved our ability to scale up our disease modeling efforts. The saRNA-based single-shot protocol is incredibly robust and repeatable, allowing us to generate consistent, large batches of iPSCs without the batch-to-batch variability we experienced with older episomal systems."

    — Dr. Jennifer Martin (6 weeks ago)

FAQs

Why is mRNA reprogramming considered safer than other non-integrating methods like episomal vectors?

While both are non-integrating, mRNA is inherently safer because it never enters the cell nucleus and is rapidly degraded in the cytoplasm, guaranteeing a true "footprint-free" status. Episomal vectors are DNA-based and, while designed not to integrate, still carry a low but detectable risk of genomic recombination, requiring more intensive, costly screening to confirm their clearance.

How do you achieve high efficiency when mRNA is transiently expressed, requiring frequent transfections?

Creative Biolabs addresses this in two ways: first, our nucleoside-modified mRNA is far more stable and efficiently translated than standard RNA, maximizing protein output per transfection. Second, we offer specialized Self-Amplifying RNA (saRNA), which self-replicates in the cytoplasm, achieving a sustained, high-level expression burst from a single delivery, dramatically boosting efficiency.

Can your Custom mRNA based Cell Reprogramming Services be used to create allogeneic ("off-the-shelf") cell therapies?

Absolutely. Our platform is ideal for allogeneic approaches. We can leverage mRNA-delivered gene-editing components to conduct targeted HLA gene editing on cell lines during the reprogramming or modification phase. This creates "universal donor" cell lines by reducing immunogenicity, which is essential for mass-market, off-the-shelf therapeutic development.

What starting cell types are compatible with your mRNA reprogramming service?

Our protocols are highly versatile and optimized for a wide range of clinically relevant starting cells, including T cells, B cells, Dendritic cells, Fibroblasts, and PBMCs. We tailor the delivery mechanism (e.g., LNP formulation or electroporation parameters) to ensure maximum viability and efficiency for your specific source material.

We are concerned about the cost and complexity of scaling up a new reprogramming process. How does your service help with industrialization?

Our service significantly reduces industrial complexity. The use of saRNA reduces labor (fewer transfections), while our high-efficiency protocols increase yield, lowering the cost per clinical-grade cell line. Furthermore, we provide standardized, cGMP-compatible synthetic mRNA, ensuring consistency and easier regulatory compliance for large-scale manufacturing.

Creative Biolabs is dedicated to accelerating your transition from scientific discovery to a safe, scalable, and functionally superior cell therapy product. Our Custom mRNA based Cell Reprogramming Services are the definitive solution for achieving footprint-free genomic safety and industrial-grade efficiency.

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Reference

  1. Nakagawa, Masato, et al. "MDM4 enables efficient human iPS cell generation from PBMCs using synthetic RNAs." Scientific Reports 15.1 (2025): 30620. https://doi.org/10.1038/s41598-025-16446-y. Distributed under Open Access license CC BY 4.0, without modification.
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