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Silence™ CAR Design & Construction Services

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Silence™ CAR-T Cell Platform

RNA interference (RNAi) is an excellent technology for functional gene silencing. To overcome the challenges in CAR-T therapy, genetic modification of CAR T cells by RNAi is a promising strategy. As the leader in CAR-T therapies, Creative Biolabs combines the CAR-T platform with RNAi-based gene silence technologies to develop next-generation strategies for advances in CAR-T therapy. We carry out a novel approach in which a miRNA or shRNA cassette is integrated into CAR-expressing retroviral vectors to generate an optimal therapeutic T cell phenotype.

Example of blockage of PD-1 in CAR-T cells by shRNA technologies.Fig.1 Example of blockage of PD-1 in CAR-T cells by shRNA technologies.1

We have developed the following novel strategies to modulate and knockdown gene expression in our CAR T-cell:

  • shRNA in a CAR T Cell Platform
    shRNA technology has been applied to modulate and knock down gene expression in CAR T-cell therapy. At Creative Biolabs, we design single shRNA or multiplexed shRNA integrated into a CAR vector to knock down the expression of single/multiple genes in CAR T cells. For example, modifying the CAR-T cells by shRNA silencing technology blocks the immune checkpoint immunosuppression axis.
  • miRNA in a CAR T Cell Platform
    miRNAs are important molecular regulators involved in many aspects of cellular processes. The manipulation of miRNA expression is an ideal approach for the improvement of T cell function. At Creative Biolabs, we provide an effective strategy to regulate CAR-T cell performance by expressing miRNAs within CAR-T cells. The selected artificial miRNA and CAR are encoded within a single DNA cassette.

All-in-one Silence™ CAR Design

Silence™ CAR construct is an all-in-one vector containing the silencer (shRNAs or miRNAs), the CAR, the cell selection marker, and therapeutic add-ons.

  • shRNA design and prediction using bioinformatic analysis
  • Tailor-made shRNA/miRNA synthesis services
  • Screening and validation of silencers knockdown rates to maximize specificity and reduce off-targets
  • Gene silencers consist of one or more target-specific nucleotide sequences
  • Optimization of vector components (promoters, fluorescent and drug-selection markers)

All-in-one Silence™ CAR vector.Fig.2 All-in-one Silence™ CAR vector.

Service Highlights

  • Rational design and optimization of CAR-T constructs with RNAi-mediated knockdown capabilities.
  • The optimal expression of candidate shRNA/miRNAs alongside a CAR construct.
  • An all-in-one vector keeps costs down effectively and improves the efficiency of gene delivery.
  • Downstream services are available, including plasmid, lentiviral vector, and cell delivery.

More Services

At Creative Biolabs, we provide one-stop Silence™ CAR-T services covering the entire Silence™ CAR-T therapy development process. We evaluate the expression of silence target genes by PCR, western blot, and FC. We also provide a comprehensive set of in vitro and in vivo functional assays to meet your academic or clinical purposes. Feel free to contact us to customize services to suit your research needs.

Reference

  1. Zhou, J.E.; et al. ShRNA-mediated silencing of PD-1 augments the efficacy of chimeric antigen receptor T cells on subcutaneous prostate and leukemia xenograft. Biomedicine & Pharmacotherapy. 2021,137: 111339.
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