shRCAR Design & Construction Service

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

shRNA Technology in CAR-T Cell

The clinical efficacy of CAR T-cell technology has been proven in the setting of human cancer, but there are many limitations to accessing this technology, such as cytokine release syndrome (CRS), the immunosuppressive mechanism in the tumor microenvironment, and T-cell exhaustion. shRNA provides a fast and efficient means of knocking down gene expression and the possibility of prolonged gene silencing. The introduction of shRNA cassettes into a CAR vector will help address the several current unmet needs in CAR T-cell therapy and empower the potential of CAR-T cell immunotherapies. At Creative Biolabs, our Research and Development Team is actively dedicated to developing safe and effective treatments for a range of different cancers. We utilize shRNA technology to improve the effect of CAR-T cells and expand the application of CAR-T therapy.

Service Details

Creative Biolabs provides one-stop shRCAR cell development services. We can clone your desired shRNA sequences into our custom-designed CAR vectors. Plasmid DNA preparation, virus packaging, and shRCAR cell generation can be purchased upon finishing the designs of shRCAR vectors.

There are two modes of service:

Self-design: Customers specify the shRNA sequences, and Creative Biolabs synthesizes and constructs the plasmid.
Creative Biolabs-design: Our team designs the shRNA targeting the gene of interest using our proprietary algorithm.

What We Can Provide

Custom shRCAR vectors
Custom shRNA design—any shRNA targeting your gene of interest.
Multiple vector selection: Lentiviral, Retroviral, or AAV
shRCAR virus packaging
We offer premium quality virus packaging services to generate shRCAR virus with high titer.
shRCAR T cell generation
shRCAR T cell in vitro assay

Creative Biolabs can design and perform a full range of validation assay services, such as the identification of silenced targets in CAR-T cells, cytokine release test, cytotoxicity test, and cell proliferation test.

Strategies of shRCAR Development

Silence of the cytokine gene to improve the safety of CAR-T therapy.
Silence of the immune checkpoint gene to reactivate T cells and increase tumor-killing ability
Manipulation of the epigenetic regulators to improve tumor immunogenicity and promote T-cell infiltration

Support Data

Data 1: PD-1 silence to improve the proliferation and anti-tumor effect of CAR-T cells

The gene of interest: PD-1

CAR: CD19 CAR and PSCA CAR

Vector: Lentivirus vector

CAR generation: Third-generation CAR-T cells

Fig.1 PD-1 silence enhances anti-tumor efficacy in CAR-T cells.¹

Data 2: GM-CSF silence to improve the safe of CAR-T cells without damaging the cytotoxicity

The gene of interest: GM-CSF

CAR: CD19 CAR

Vector: Lentivirus vector

CAR generation: Second-generation CAR-T cells

Fig.2 GM-CSF silence reduces the secretion of multiple inflammatory cytokines without damaging the cytotoxicity.²

References

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.
Shang, S.; et al. RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines. Investigational New Drugs. 2023, 41(2): 220-5.