CRISPR-Cas9 Immunogenicity Testing

PhIP-Seq Assays Identify Immune Response to CRISPR-Cas9 Treatment

We develop high-throughput, cost-effective custom PhIP-Seq assays

CRISPR-Cas9 technology has revolutionized genome editing, offering precise and efficient genetic modifications. However, like other biotherapeutics, the immunogenicity of CRISPR-Cas9 is a critical factor influencing its safety and efficacy. Immunogenicity testing is essential to assess the potential for the immune system to recognize CRISPR-Cas9 components as foreign and mount an immune response.

Immunogenic responses to CRISPR-Cas9 can reduce therapeutic efficacy, lead to adverse immune reactions, or limit re-dosing potential. Therefore, robust immunogenicity testing strategies are vital for the development and clinical application of CRISPR-based therapeutics. The humoral immune response involves the production of antibodies, including anti-drug antibodies (ADAs), against the CRISPR-Cas9 components. This is particularly relevant for the Cas9 protein, derived from bacterial sources such as Streptococcus pyogenes or Staphylococcus aureus, which may be recognized as foreign.

Factors Influencing Immunogenicity

• Source of Cas9: Different bacterial sources may vary in immunogenicity due to the presence of distinct epitopes.
• Pre-existing Immunity: Individuals exposed to Cas9-producing bacteria may already have antibodies or memory T cells against Cas9.

ADAs generated in response to CRISPR-Cas9 treatment can be identified using a custom PhIP-Seq assay (library), which would include sufficient overlapping peptide inserts that would allow not only high-level immunogenicity to be identified, but it could also identify the specific component of the treatment that has elicited the response.

Our unique CRO services provide the experience and expertise necessary to develop high-throughput, cost-effective custom assays that help detect immune responses to CRISPR-Cas9 treatment. Our innovative approach ensures accurate identification of immune reactions, enabling researchers to advance their studies with confidence and efficiency.