The Doubleedge Sword Of CRISPR Application For In Vivo Studies

A new editorial entitled "Dual Applications of CRISPR for In Vivo Research" is published in Oncotarget .

In this new article, Aarhus University researcher Martin K. Thomsen begins his editorial by discussing a seminal paper ten years ago on the in vivo application of multiple regularly interspersed short palindromic repeats (CRISPRs) to cancer in different organs by Platt et al. mousey

This landmark article describes advances in the delivery of tissue-targeted sgRNAs to generate loss- and gain-of-function mutations without the need for timely backcrossing of mouse genetic lines. In addition, studies have shown that multiplexing is possible, allowing the method to target multiple sites at the same time. This technology was supposed to revolutionize the way mouse cancer models were created, but even 10 years later, few studies referred to this method.

"A double-edged sword of using CRISPR in vivo is the lack of generation of mutations in the target sequence," Thomsen wrote.

Because CRISPR causes mutations, they do not always occur, resulting in cells lacking the desired mutation. This is further complicated by different types of indels, which can result in a functional protein with only a few amino acid changes without introducing a premature stop codon. This leads to clone-to-clone variation and results in tumors with different mutational profiles. However, this is an advantage of CRISPR for the development of in vivo cancer models, as natural selection will occur and cause the Darwinian evolution of cancer.

"Overall, CRISPR in vivo applications will become more widespread, although the method has its challenges, in the future it will become more feasible and allow more researchers to use this technology," concluded Thomsen.

Provided by Impact Journals LLC

Artificial intelligence and genetic engineering, Dr. Fazle Rana