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PETBioNewsNewsHuman immune response may stymie CRISPR genome editing therapies

BioNews

Human immune response may stymie CRISPR genome editing therapies

Published 29 January 2018 posted in News and appears in BioNews 933

Author

Rikita Patel

Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the output from a DNA sequencing machine.
CC BY 4.0
Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the sequencing output from an automated DNA sequencing machine.

The human adaptive immune response against the Cas9 protein - part of the CRISPR genome editing system — may pose a barrier to new therapies, suggests a new study...

The human adaptive immune response against the Cas9 protein – part of the CRISPR/Cas9 genome editing system – may pose a barrier to new therapies, suggests a new study.

'This was a fully expected observation, since we are all constantly exposed to many microbes,' Professor George Church, a geneticist at Harvard Medical School, who was not involved in the study, told Gizmodo.

Results from the study – published in 'pre-print' form on bioRxiv, and yet to be peer-reviewed – found pre-existing antibodies against Cas9 derived from two common bacterial species in 22 newborns and 12 healthy adults.

Antibodies against Cas9 derived from Staphlococcus aureus and Streptococcus pyogenes, were found in the blood serum of 79 and 65 percent of study participants respectively.

The study authors bring attention to the possible, systemic side effects of CRISPR/Cas9 that should be addressed before tests are carried out on humans. 'Like any new technology, you want to identify potential problems and engineer solutions for them,' Dr Matthew Porteus, study author at Stanford University in California, told STAT. 'This is an issue that should be addressed.'

The study also looked at T-cell response in blood from 13 healthy adults and found that 46 percent of them produced T-cells against Cas9 from Staphlococcus aureus,but not Streptococcus pyogenes.

The presence of Cas9 specific T-cells could lead to 'significant toxicity' say the study authors and other safety risks associated with the technique are still in question (see BioNews 903).

Solutions to overcome barriers to harnessing genome editing therapies have been proposed, including the use of Cas9 proteins from other bacteria, editing cells ex vivo, or even producing new delivery vectors that are invisible to the human defence system.

'New Cas editing enzymes are being described all the time from bacterial species that are not human pathogens (and so there would be no chance to develop the pre-existing antibodies),' Professor Jacob Corn, from University of California, Berkeley, who was not involved in the study, told STAT.

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