Immunogenicity of CRISPR therapeutics-Critical considerations for clinical translation

Radwa Ewaisha; Karen S Anderson

doi:10.3389/fbioe.2023.1138596

Immunogenicity of CRISPR therapeutics-Critical considerations for clinical translation

Front Bioeng Biotechnol. 2023 Feb 16:11:1138596. doi: 10.3389/fbioe.2023.1138596. eCollection 2023.

Authors

Radwa Ewaisha^{1

2}, Karen S Anderson³

Affiliations

¹ Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
² Department of Microbiology and Immunology, School of Pharmacy, Newgiza University, Newgiza, Egypt.
³ Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, United States.

Abstract

CRISPR offers new hope for many patients and promises to transform the way we think of future therapies. Ensuring safety of CRISPR therapeutics is a top priority for clinical translation and specific recommendations have been recently released by the FDA. Rapid progress in the preclinical and clinical development of CRISPR therapeutics leverages years of experience with gene therapy successes and failures. Adverse events due to immunogenicity have been a major setback that has impacted the field of gene therapy. As several in vivo CRISPR clinical trials make progress, the challenge of immunogenicity remains a significant roadblock to the clinical availability and utility of CRISPR therapeutics. In this review, we examine what is currently known about the immunogenicity of CRISPR therapeutics and discuss several considerations to mitigate immunogenicity for the design of safe and clinically translatable CRISPR therapeutics.

Keywords: CRISPR-Cas; Cas9; clinical translation; clinical trials; gene therapy; genome editing; immunogenicity.

Publication types

Review