Prevalence of Pre-existing Antibodies to CRISPR-Associated Nuclease Cas9 in the USA Population.
Mol Ther Methods Clin Dev
; 10: 105-112, 2018 Sep 21.
Article
in En
| MEDLINE
| ID: mdl-30073181
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prevalence_studies
/
Risk_factors_studies
Language:
En
Journal:
Mol Ther Methods Clin Dev
Year:
2018
Document type:
Article
Affiliation country:
United States