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Study suggests 96 percent of people 'immune' to CRISPR/Cas9

5 November 2018
Appeared in BioNews 974

The genome editing approach, CRISPR/Cas9, may not be as successful in humans as hoped.

A study published in Nature Medicine highlights that the human immune system may be able to recognise fragments of the Cas9 enzyme, causing the destruction of cells that have been subjected to genome editing. 

'The Cas9 protein, which is derived from Streptococcus bacteria, forms an integral part of the CRISPR/Cas9 system. As streptococcal infections are common in humans, we hypothesised that there might be a pre-existing immunological memory to Cas9,' said Dr Michael Schmueck-Henneresse at Charité University Medicine in Berlin, Germany, and lead scientist on the study.

Of the 48 participants, 96 percent showed pre-existing immunity to Cas9. These healthy volunteers had T effector cells – cells with a biological memory that are part of the adaptive immune response – that reacted to Cas9. These cells cause damage upon activation as they are responding to infections. This not only causes a problem for the efficiency of any CRISPR/Cas9 genome editing therapies, as genetically-manipulated cells will be targeted for destruction, but also the accompanying immune response may cause second-hand damage to healthy tissue.

The authors of this study included data to show that cells that function as regulators of T effector cells (T regulatory cells) may suppress unwanted immune responses and so could be used alongside CRISPR/Cas9 based therapies.

The CRISPR/Cas9 genome editing system may offer a plethora of therapeutic applications, however, scientists are becoming more aware of complexities that may render this system unsuitable for use in humans. This study supports previous results found by researchers from Stanford University in California, which found pre-existing antibodies against Cas9 (see BioNews 933).

CRISPR/Cas9 relies on the adaptation of a naturally occurring process in bacteria. Bacteria are able to cut viral DNA from their genomes to fight the invasions. By harnessing this biological process, scientists have been able to effectively and efficiently modify the DNA of live cells and organisms. The Cas9 unit is crucial to the process as it is the enzyme used to enforce double-strand DNA breaks. Most variations of this enzyme are adapted from common infectious bacteria and so may pose similar risks to Cas9 extracted from S. pyogenes

Are we immune to the CRISPR-Cas9 gene editing scissors?
EurekAlert |  30 October 2018
High prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population
Nature Medicine |  29 October 2018
Pre-Existing Immunity to CRISPR Found in 96% of People in Study
Xconomy |  29 October 2018
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