Over the past 15 years, developments in the gene-editing technique known as CRISPR-Cas9 have produced significant new understandings of the functions that particular genes play in a variety of disorders.
However, as of right now, this method, which enables researchers to alter DNA sequences and analyze the results by using a “guide” RNA, can only target, delete, replace, or edit a single gene sequence using a single guide RNA and has limited capacity to evaluate many genetic modifications at once.
However, using CRISPR (“clustered regularly interspaced short palindromic repeats”) technology, Yale researchers have created several advanced mouse models that enable them to evaluate genetic interactions on a variety of immunological responses to various diseases, including cancer, at the same time.
The study was published in the journal Nature Biomedical Engineering.
By using enzymes, such as Cas9 (CRISPR-associated protein 9), as a kind of molecular scissors, gene editing methods enable researchers to precisely cut or alter segments of DNA or RNA, providing information about the part these genes play in a range of illnesses.
Researchers claimed that the new technique, known as CRISPR-Cas12a, can assist them in evaluating the effects of several genetic alterations involved in various immune system responses at the same time.
We have created four new Cas12a mouse lines that will allow researchers to study complex genetic interactions and their effects involved in many disorders.”
Sidi Chen, Associate Professor and Study Co-Corresponding Author, Genetics and Neurosurgery, Yale School of Medicine
These potent tool strains allowed Chen's lab to simultaneously fine-tune sets of genes in multiple directions and cause and monitor alterations in a range of immune system cells in response to gene editing. Additionally, the lab facilitated the quick development of novel disease and treatment models, including skin cancer, lung cancer, and genetic liver disease.
According to him, this development will provide researchers developing novel treatments for a variety of illnesses, including cancer, metabolic diseases, autoimmune diseases, and neurological conditions.
Source:
Journal reference:
Tang, K., et al. (2025) Cas12a-knock-in mice for multiplexed genome editing, disease modeling, and immune-cell engineering. Nature Biomedical Engineering. doi.org/10.1038/s41551-025-01371-2.