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Mol Ther Methods Clin Dev 2018 Jun 15;10:105-12

Prevalence of pre-existing antibodies to CRISPR-associated nuclease Cas9 in the USA population.

Simhadri VL, McGill J, McMahon S, Wang J, Jiang H, Sauna ZE

Abstract

The repurposing of the CRISPR/Cas microbial adaptive immune system for gene editing has resulted in an exponential rise in new technologies and promising approaches for treating numerous human diseases. While some of the approaches being currently developed involve ex vivo editing by CRISPR/Cas9, many more potential applications will require in vivo editing. The in vivo use of this technology comes with challenges, one of which is the immune response to Cas9, a protein of microbial origin. Thus, the prevalence of pre-existing antibodies to Cas9 could also be a relevant parameter. There are many avenues for how CRISPR/Cas9 technologies will be applied in vivo, including the mode of delivery. These may be expected to invoke different immunological pathways. Nonetheless, as with all protein therapeutics, it may be desirable to monitor for anti-Cas9 antibodies during clinical development. This will require the development of robust and reliable assays. Here, we describe ELISA-based assays that are capable of detecting antibodies to Cas9 from Staphylococcus aureus (SaCas9) and Streptococcs pyogenes (SpCas9) in human sera. Furthermore, using these assays to screen for pre-existing antibodies in 200 human serum samples, we found the prevalence of anti-SaCas9 and anti-SpCas9 antibodies to be 10% and 2.5%, respectively.


Category: Journal Article
PubMed ID: #30073181 DOI: 10.1016/j.omtm.2018.06.006
PubMed Central ID: #PMC6070699
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2018-03-25 Entry Last Modified: 2018-12-09
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