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21.12.2019 |

Here’s Why Many CRISPR/Cas9 Experiments Could Be Wrong – and How to Fix Them

Researchers assumed that CRISPR was turning off genes. They shouldn’t have.

Every living cell on Earth has proteins. Typically thousands of them, that serve as molecular machines to digest food, sense the environment, or anything else a cell must do. However, many genes, and the proteins they code for, have unknown functions. In humans, the function of about 1 out of 5 of genes is unknown. To explore these dark corners of the genome, scientists can break up DNA to disable a gene, making their encoded proteins nonfunctional, and watch what happens to cells as a result, inferring the lost function from what goes wrong.

When CRISPR/Cas9 came online in 2012, it offered scientists a tool to do exactly this – cut genes. The Cas9 enzyme searches through DNA, using a “guide RNA” to look for a specific sequence, and makes a cut when it finds a match. The gene, split in two, is repaired by the cell, but often with a large chunk missing. Many scientists assume that if a chunk of a gene is missing then the protein that it encodes will not function, or even be produced.

In many cases, they would be terribly wrong.

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