Custom B Cell Reprogramming by mRNA

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Custom B Cell Reprogramming by mRNA

B cell reprogramming refers to the ability to redefine the identity of B cell by changing its epigenetic and transcriptional landscapes, reflected in the acquisition of new morphological, molecular, and functional features. At Creative Biolabs, you can gain access to the most rapid integration-free B cell reprogramming method on the market. Our RNA technology has been used across a diverse range of B cell projects in the research community, from enhancing in vivo research models to optimizing human B cell reprogramming. Creative Biolabs now provides customized B cell reprogramming services to our honored clients.

B Cell-based Vaccine Design

Most vaccines provide protection from infection through the generation of neutralizing antibody (nAb). The repertoire of B cells responding to immunization is the starting material from which nAb eventually arises. As Fig.1 shown below, single B cell sorting and culturing in the presence of feeder cells allow direct screening and selection of naturally produced antibodies with desired functionality and recovery of the corresponding immunoglobulin (Ig) gene sequence. In turn, repertoire analyses to understand the origin and evolution of the antibodies of interest can be performed. Starting from the recovered sequences, further expression of the recombinant antibodies of interest in the most appropriate system allows for a fine-tuned characterization of their properties. Structural characterization of such antibodies bound to their target antigen allows for the detailed definition of the protective epitope. The protective epitope highlighted in red can then be engineered for presentation as an optimized immunogen in a novel format such as nanoparticle. The resulting new antigen can be developed with the best formulation or delivery system to then be tested in humans.

Interplay of B cell technology and structural biology in vaccine design. Fig.1 Interplay of B cell technology and structural biology in vaccine design. (Rappuoli, 2016)

B Cell Reprogramming by mRNA

B cells are refractory to reprogramming. For difficult-to-reprogram cells or to overcome antiviral response resistance during cell reprogramming, a possible effective experimental alternative is the use of individual capped mRNA constructs. These reprogramming mRNAs mimic fully processed mature mRNAs encoding for reprogramming factors. Normal B cells could be reprogrammed by enforced expression of some specific transcription factors. For instance, mature B cells can be reprogrammed into erythroid lineage by expressing various hematopoietic transcription factors. Among various factors, GATA-1, SCL together with CCAAT/enhancer binding protein α (EBPα) turns out to be a minimal set of factors that efficiently reprogrammed terminally differentiated mature B cells into the erythroid lineage. Others have presented reprogramming of B cell progenitors into macrophages by C/EBPα.

Interplay of B cell technology and structural biology in vaccine design. Fig.2 Origins and fate potential for mature B lymphoid cells. (Boothby, 2019)

What Can We Do for You?

Creative Biolabs has identified transcription factors combination to reprogram B lymphocytes and our experiences indicate that specific combinations of reprogramming factors can reset the genome of B cell material. The reprogrammed B cells will carry the genetic rearrangements characteristic brought by introduced mRNA. The benefits of our mRNA reprogramming include:

  • Footprint-free: mRNA vectors are rapidly degraded 48 hours following transfection.
  • Integration-free: No DNA is used during reprogramming, eliminating the risk of genomic integration of reprogramming factors or vector sequences.
  • Efficient: RNA reprogramming is highly efficient, requiring fewer starting target cells than other methods.
  • Rapid: RNA reprogramming provides rapid access for projects where timing is critical.
Interplay of B cell technology and structural biology in vaccine design.

Whether you have your cells that require reprogramming or wish to source tissues from a select patient group, experts at Creative Biolabs have the resources and expertise to achieve your research goals. You can contact us for custom B cell reprogramming services here or find out more on our website.

Reference

  1. Rappuoli, R.; et al. Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design. Journal of Experimental Medicine. 2016, 213(4): 469-481.
  2. Boothby, M. R.; et al. Molecular regulation of peripheral B cells and their progeny in immunity. Genes & development. 2019, 33(1-2): 26-48.
For Research Use Only.