A team of researchers has introduced an innovative approach to modify DNA within cells more precisely and efficiently by simultaneously editing multiple locations with a single tool. By utilizing specialized molecules known as retrons, they have developed multitrons, a method that can effectively alter DNA in various organisms like bacteria, yeast, and human cells.
Genome editing has revolutionized the scientific field by allowing researchers to manipulate DNA in cells, enabling the study of diseases and the development of potential therapies to address genetic mutations. Traditionally, editing cells one at a time has been the norm, limiting the scope of genetic modifications that can be made.
The team at Gladstone Institutes, led by Associate Investigator Seth Shipman, PhD, embarked on this groundbreaking method to delve into the intricate complexities of biology and disease. Their latest study, published in Nature Chemical Biology, presents their innovative technique.
Conquering Limitations
Shipman’s lab is at the forefront of retrons research, leveraging these molecular components from a bacterial immune system to enhance DNA manipulation. In their recent breakthrough, they combined retrons with CRISPR-Cas9 technology to swiftly edit human cells with high efficiency.
The team aimed to address a key drawback of current genome editing methods with their latest study.
Previously, editing multiple genomic locations apart from each other involved a laborious process of sequential edits. The introduction of multitrons revolutionizes this by generating diverse DNA segments within a cell simultaneously.
One advantage of multitrons is their ability to delete significant genome segments efficiently.
González-Delgado explains, “Multitrons streamline the editing process by sequentially deleting portions of the genome, effectively erasing sections until the targeted region is completely removed.”
Many Potential Applications
The study unveiled immediate applications for multitrons in molecular recording and metabolic engineering.
Retrons have previously been used to document cellular events and environmental changes. Now, with multitrons, researchers can enhance the sensitivity and range of molecular recordings.
González-Delgado emphasizes, “The versatility of multitrons allows us to capture both subtle and prominent signals concurrently, expanding our recording capabilities. This could potentially be applied in monitoring signals like inflammation in the gut microbiome.”
In terms of metabolic engineering, multitrons were utilized to edit multiple genes in a metabolic pathway simultaneously, leading to a significant increase in the production of substances like lycopene, a potent antioxidant.
Shipman envisions, “The ability to introduce numerous genetic mutations simultaneously is crucial for modeling complex diseases and developing potential treatments. Our innovative approach marks a significant stride in this direction.”
