CRISPR-Cas9 gene editing tool can cause chromothripsis leading to oncogenes

CRISPER-Cas9 an ancient immune system in bacterium
Microbiologist in 1993 identified some unique repetitive, well preserved DNA sequences in Prokaryotes, appearing over and over again. Between repetitive  DNA sequences there are unique sequences that differs. These repetitive sequences are called as 'clustered regularly interspaced short palindromic repeats', abbreviated as CRISPER. Those non repetitive sequences matches with the genome of their pathogenic phage viruses. "So the hypothesis were put forward that bacterium succeeded in surviving from the virus infection by adding a piece of virus genetic code into it's genome as the memory of the infection. Perhaps the mechanism used by bacterium to neutralize a virus is by RNA interference." These were named as trans-activating crispr RNA (tracrRNA). That's an ancient immune system that protects bacterium from the infection of viruses.

Genetic scissor

Emmanuelle Charpentier and Jennifer Doudna, found that apart from CRISPER there are special CRISPER associated (cas9) genes, known for coding of a protein which unwinds and cleaves DNA (perhaps for the virus genetic material). Both scientists realized that the CRISPER-cas9 system could be programmed to cut other pieces of DNA and were awarded Nobel Prize 2020 in Chemistry "for the development of a method for genome editing". This precise molecular tool, like a scissor to make precise incision in DNA , to rewrite the code of life i.e. the genetic material.

Emmanuelle (left) and Jennifer (right)
Thankfully shared from Nobel Media in public domain

It also raises ethical, social and safety concerns as it's controversial use on human cells. This genetic scissor opened a new era of possibilities in the field of life sciences, biochemistry, cell biology, like as a gene editor, knowing the functions of genes and editing them for desired characters in plant breeding or controlling hereditary diseases etc.

CRISPER-Cas9 and genotoxicity

CRISPER-Cas9 based therapies have reported many genotoxic incident causing clinical complications like large scale DNA deletions, p53 tumor suppressor protein, chromosomal truncations, preexisting antibodies and T cells induced problems.

This happens because in clinical applications the possible safety concern and care are not being taken, resulting in break of d-DNA that results in genomic rearrangement, that means individual arrangement of chromosome is shattered which may also result in subsequent rejoining in haphazard order.

It is found that mostly cells do not survive due to these alterations and if they do, then may result in oncogenic fusion proteins or dysregulated expression of a particular gene that may bring more unwanted complications in individual cell.