Thursday, April 15, 2021

Recently Discovered Side Effect of CRISPR Gene Editing

    CRISPR, short for clustered regularly interspaced short palindromic repeats, are found in prokaryotic genomes; they have nucleotide repeats and spacers. Associated with this family of DNA is Cas-9, which is an enzyme that has the ability to cut strands of DNA.

    Separate studies concluded that the Cas-9 enzyme can be directed to cut any region of DNA by changing crRNA's (CRISPR RNA) nucleotide sequence; fusing this with tracrRNA (trans-activating RNA) forms a guide RNA. George Church, a genetics professor at Harvard Medical School, stated "the [guide] RNA plus the protein [Cas-9] will cut -- like a pair of scissors -- the DNA at that site, and ideally nowhere else." After the region is cut, the cell will naturally repair this; this may introduce mutations or other changes.

    This genome editing tool is powerful. Diseases-causing mutations may be corrected in embryos to prevent future genetic disorders. Use of CRISPR-Cas9 may improve fertility treatments for couples with disease-causing mutations. Problems arise when the Cas-9 protein breaks a double strand (DSB induction). To repair this, microhomology-mediated end joining occurs; the occurs in the first cell cycle of the zygote, restoring the reading frames. In this process, half of the breaks remain unrepaired; a paternal allele is undetectable. After mitosis, chromosomes are lost.

These mutations provide significant challenges for correction.

1 comment:

  1. Some years ago I remember being amazed when learning about the efficient gene editing through the CRISPR-cas9 mechanism. I recall that the only cons were common deletion and insertion mutations. The complications caused by the cas9 protein breaking a double strand are quite alarming. Since the repair process still leaves half of the breaks unresolved, the reliability of the CRISPR-cas9 system seems rather questionable.