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Custom mRNA based B Cell Reprogramming Service

Introduction mRNA based B Cell Reprogramming Workflow What We Can Offer FAQ

Introduction

Our Custom mRNA-based B Cell Reprogramming Service leverages B cell plasticity—driven by deleting master regulators like Pax5 and expressing TFs such as C/EBPα—to transdifferentiate B cells into macrophages, erythroid cells, etc. We use stable modified mRNA for transient TF expression, enabling rapid, genome-unaltered cell fate conversion.

Offering integration-free technology and high-efficiency delivery, we accelerate patient-derived immune cell engineering. Our targeted solutions overcome B cell plasticity and reprogramming challenges, delivering high-purity functional cells for therapeutics or research, with safer, faster paths to clinical candidates.

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Custom mRNA based B Cell Reprogramming Service

B cells possess both anti-tumor properties and tumor-promoting effects in the tumor microenvironment (OA Literature) Fig.1 The dual characteristics of B cells in the tumor microenvironment of cancer. Its anti-tumor properties can be used to enhance the targets of immunotherapy.1

B Cell Reprogramming: The Mechanism of Lineage Switching

B cell reprogramming hinges on overriding the established transcriptional programs maintained by key factors like Pax5 and EBF1. By transiently delivering specific, powerful TFs via mRNA, we induce a rapid epigenetic reset. For instance, delivering C/EBPα causes the silencing of B-lymphocyte genes and the activation of macrophage-specific genes, resulting in the complete and highly efficient conversion of the cell's identity. This transdifferentiation is distinct from generating iPSCs (though possible), as it often results in a direct switch to a committed lineage, preserving specific features like the original Immunoglobulin (Ig) gene rearrangements, which is invaluable for certain immunological studies.

Advantages of mRNA Delivery

The core advantage lies in bypassing the safety and complexity challenges of traditional DNA- or retrovirus-based methods.

  • Footprint-Free: The delivered mRNA is fully degraded shortly after delivering its transient instructional payload, leaving no permanent trace in the host genome.
  • High Control: Transfection conditions (mRNA dose, time) can be precisely adjusted to control the duration and level of transcription factor expression, allowing fine-tuning of the reprogramming process.
  • Scalability and Purity: The high efficiency of the mRNA platform leads to superior scalability and a higher percentage of correctly reprogrammed cells, simplifying downstream purification.

Application of Reprogrammed B Cells

The functional cells generated through this service have vast potential in:

  1. Immunotherapy & Vaccines: Generating autologous macrophages or dendritic cells for use as powerful antigen-presenting cells (APCs), or producing patient-specific NK or T cell populations from B cell-derived iPSCs.
  2. Regenerative Medicine: Creating patient-matched cells (e.g., erythroid lineage cells) for in vitro disease modeling, drug screening, or potentially autologous cell replacement therapies.
  3. Disease Modeling: Developing accurate in vitro models by generating cells from patient-derived B cells that carry specific disease-related mutations.

Workflow

We offer a comprehensive, streamlined, and scalable process designed for maximum transparency and efficiency, ensuring high-quality, functional cell outputs tailored to your specific research needs.

Required Starting Materials

  • B Cell Source Material (e.g., purified B lymphocytes, PBMCs, patient tissue samples)
  • Target Cell Lineage (e.g., macrophage, erythroid, iPSC)
  • Custom Reprogramming Factor Sequences (if applicable)
Materials
mRNA Design

mRNA Design and Optimization

Conduct custom sequence design, codon optimization, incorporation of modified nucleotides (e.g., Pseudouridine, N6-Methyladenosine), and 5' capping (e.g., ARCA).

Delivery Vehicle Engineering

Design and synthesize customized lipid formulations, including Lipid Nanoparticles (LNPs), for mRNA payload delivery.

LNP Engineering
Transfection

High-Efficiency Cell Transfection

Optimize transfection parameters (dose, timing, vehicle ratio) tailored to specific B cell source material.

Lineage Conversion and Culture

Maintain sustained culture in specialized media under defined conditions, withdrawing B cell survival factors and adding lineage-specific factors (e.g., macrophage growth factors).

Culture
QC

Purification and Quality Control

Sort or select converted cells, followed by rigorous QC for viability, purity, and functional validation (e.g., phagocytosis assays for macrophages).

Final Deliverables

  • Detailed Reprogramming Protocol: Step-by-step instructions for scale-up and culture
  • Characterization Data Report: Flow cytometry, phenotype analysis (e.g., Mac-1, F4/80 for macrophages), and functional assays
  • Reprogrammed Cell Samples: High-purity batches of the desired cell lineage (e.g., B cell-derived macrophages)

Estimated Timeframe: 6–12 weeks, depending on the complexity of the target lineage and the required cell output scale.

Deliverables

What We Can Offer

Creative Biolabs is a true one-stop solution for Custom mRNA-based B-cell reprogramming Services. We recognize that every cell engineering project is unique, requiring meticulous customization. Our advanced capabilities ensure seamless transition from initial concept to validated, functional cell output.

One-Stop Reprogramming Solution
Comprehensive service covering custom mRNA design, synthesis, optimization, LNP formulation, and final functional validation.

Custom Transcription Factor Combinations
Test and implement specialized TF cocktails (e.g., C/EBPα, GATA-1, SCL, OKSM) tailored to generate target cell lineages.

Advanced mRNA Engineering & Optimization
Custom mRNA modifications (e.g., Pseudouridine, ARCA capping) ensure maximum stability and translational efficiency in primary B cells.

Proprietary Delivery System Development
Custom LNPs/lipoplexes engineered for optimized B cell transfection, overcoming immune cell delivery challenges.

Rigorous Quality-by-Design (QbD) Protocols
Strict PAT and quality systems throughout culture/reprogramming to ensure reproducibility and functional fidelity.

Full Functional Characterization
Custom functional assays (e.g., phagocytosis, cytokine secretion) validate reprogrammed cells' phenotype and function.

Scalable Output
Seamless scale-up from small feasibility studies to pre-clinical/large-scale in vitro screening production volumes.

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Customer Reviews

  • [Precision Engineering] "Using Creative Biolabs' Custom mRNA based B Cell Reprogramming Service in our research has significantly improved the fidelity of our trans differentiation models. The ability to use modified, integration-free mRNA allowed us to safely generate highly pure macrophage populations from B cells in a fraction of the time, overcoming the refractory nature of the starting material."

    — 2 Weeks Ago, Dr. Ashton Carter

  • [Safety Profile] "The footprint-free nature of this mRNA delivery is a crucial advantage. In our pre-IND work, eliminating the genomic integration risk associated with our prior lentiviral methods accelerated our path toward regulatory submission. We found the custom LNP formulation provided by Creative Biolabs to be exceptionally efficient."

    — 1 Month Ago, Dr. Karen H. Mitchell

  • [Process Efficiency] "Creative Biolabs' expertise in optimizing the nucleotide modification (Pseudouridine) and 5' capping (ARCA) of the reprogramming mRNA provided a remarkable boost in translation. We saw an immediate increase in the yield and viability of the resulting erythroid lineage cells derived from B cell progenitors, making our high-throughput screens finally feasible."

    — 3 Months Ago, Prof. Eric L. Thompson

FAQ

How does mRNA reprogramming compare to using lentivirus for my cell engineering project?

The primary advantage of mRNA over lentivirus is safety and speed. While lentivirus offers permanent gene integration, our mRNA method is integration-free, eliminating the risk of insertional mutagenesis, which is often a major regulatory hurdle. Additionally, the high efficiency of mRNA allows for visible lineage conversion in just a few days, dramatically speeding up your timeline.

What is the purity of the final reprogrammed cell population, and how is it validated?

We strive for the highest purity possible. Our process is optimized for high conversion rates, often resulting in yields far exceeding traditional methods. Validation is achieved using multiple methods, including flow cytometry for specific surface markers (e.g., Mac-1, F4/80, CD11b) and functional assays (e.g., phagocytosis).

My target B cell source material is limited. Is this service scalable for small samples?

Yes. RNA reprogramming is inherently more efficient than other methods, requiring fewer starting cells to achieve a successful outcome. We specialize in optimizing protocols for limited or difficult-to-reprogram primary cell sources, which is a major benefit for rare patient samples.

Can Creative Biolabs design the delivery vehicle (LNP) to target B cells in vivo?

Our expertise includes the development of custom delivery vehicles like LNPs that are engineered for high transfection efficiency. While our standard service focuses on ex vivo reprogramming, we offer advanced LNP development services tailored toward specific cell tropism, which can be adapted for in vivo applications.

How do you ensure the modified mRNA is stable and highly translated?

We use proprietary modifications in the mRNA backbone. This includes incorporating Pseudouridine to reduce immunogenicity and enhancing the 5' end with specialized caps like ARCA, ensuring the mRNA remains stable and robustly translated by the cell's machinery. This engineering is critical for the transient, high-level expression necessary for a successful lineage switch.

Creative Biolabs offers an industry-leading, integration-free platform for high-efficiency B lymphocyte transdifferentiation. Combining expertise in master transcription factors (e.g., C/EBPα), cutting-edge modified mRNA technology, and custom LNP delivery systems, we deliver safe, rapid, scalable solutions for generating functional patient-derived cells critical for research and therapeutic development.

Contact Our Team for More Information and to Discuss Your Project

Reference

  1. Gupta, Sneh Lata, et al. "B-cell-based immunotherapy: a promising new alternative." Vaccines 10.6 (2022): 879. https://doi.org/10.3390/vaccines10060879. Distributed under Open Access license CC BY 4.0, without modification.
All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.