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Topic: Immunity to Cas9 might pose a problem for CRISPR tech (Read 98 times) previous topic - next topic

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  • meepmeep
  • Administrator
  • zombiecat queen
Immunity to Cas9 might pose a problem for CRISPR tech
Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans

The CRISPR-Cas9 system has proven to be a powerful tool for genome editing allowing for the precise modification of specific DNA sequences within a cell. Many efforts are currently underway to use the CRISPR-Cas9 system for the therapeutic correction of human genetic diseases. The most widely used homologs of the Cas9 protein are derived from the bacteria Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes). Based on the fact that these two bacterial species cause infections in the human population at high frequencies, we looked for the presence of pre-existing adaptive immune responses to their respective Cas9 homologs, SaCas9 (S. aureus homolog of Cas9) and SpCas9 (S. pyogenes homolog of Cas9). To determine the presence of anti-Cas9 antibodies, we probed for the two homologs using human serum and were able to detect antibodies against both, with 79% of donors staining against SaCas9 and 65% of donors staining against SpCas9. Upon investigating the presence of antigen-specific T-cells against the two homologs in human peripheral blood, we found anti-SaCas9 T-cells in 46% of donors. Upon isolating, expanding, and conducting antigen re-stimulation experiments on several of these donors anti-SaCas9 T-cells, we observed a SaCas9-specific response confirming that these T-cells were antigen-specific. We were unable to detect antigen-specific T-cells against SpCas9, although the sensitivity of the assay precludes us from concluding that such T-cells do not exist. Together, this data demonstrates that there are pre-existing humoral and cell-mediated adaptive immune responses to Cas9 in humans, a factor which must be taken into account as the CRISPR-Cas9 system moves forward into clinical trials.

Of course, this doesn't necessarily mean any given CRISPR-Cas9 system would automatically fail. The Cas9 would need to be different enough to avoid recognition. And I doubt this would be a concern in any gene editing done at the embryonic stage.

  • osmanthus
  • Administrator
  • Fingerer of piglets
Re: Immunity to Cas9 might pose a problem for CRISPR tech
Reply #1
So we can still do evil things to babies in the womb? Cool. No worries then.
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