CRISPR is a revolutionary research tool that enables researchers to efficiently study the effect of changing genes, commonly by "knocking them out". CRISPR bas

CRISPR is a revolutionary research tool that enables researchers to efficiently study the effect of changing genes, commonly by "knocking them out". CRISPR basically cuts a specific piece of DNA from the genome, so you can study how a cell / animal / disease model is different with and without the gene -- testing causality of gene and phenotype when CRISPR knocks out a gene, the cell tries to repair the DNA using its natural dna repair mechanisms. this can lead to unexpected insertions or deletions of DNA. researchers are widely aware of this risk and have studied it however, this paper exposes shortcomings of prior assessments of this risk. specifically, prior studies thought that the unexpected insertions or deltions of DNA were usually small, less than 20 nucleotides. there were observations of larger "indels" but these were thought to be rare. there are a few other shortcomings of the research into "crispr induced lesions", the article lists them in detail the scientists suspect that prior research has significantly underestimated the level of genomic alteration induced by crispr, and that some of this alteration could cause disease like cancer the authors first tried to delete a gene with crispr by targeting the protein coding part of the gene, and also non protein coding parts. the crispr targeting the protein coding part of the gene showed significnat knockdown of the gene (over 97%). however, so did the crispr targeting the non protein coding part of the gene (up to 20% of cells did not express the gene). some crispr constructs targeted sites that were over 2,000 base pairs from the nearest protein coding site, and 5-7% of those cells did not express the gene. they determined that loss of the gene was due to loss of the protein coding region, not just regulatory elements in the non protein coding part. they did similar experiments in other cell lines and with other genes so this suggests that researchers may have wildly underestimated the amount of genetic chaos induced by crispr. it is more possible than we thought that people receiving crispr therapies may also have pathogenic crispr induced dna damage the paper references six studies, all in China, currently using crispr to treat humans. 3 of the studies use crispr to "knock out" PD1, a molecule that blocks the immune system from attacking cancer, 2 use CRISPR to make cells express CD19 to attack cancerous blood cells, and one study tests an HIV therapy. anti PD1 antibodies and anti CD19 cell therapies using other gene editing techniques are approved and highly effective. anti pd1 antibodies are expected to generate over $20B in sales in the next few years. so these treatments have strong scientific basis supporting their potential effectiveness, but we may have drasticlly underestimated the risks