Cornell researchers have built a smaller gene-editing system that can place large pieces of DNA at a chosen site in bacteria, an early result they hope can be adapted for plants, animals and people.
The laboratory work, described in an Oct. 1 Molecular Cell study and a Cornell Chronicle report, is not a treatment or a demonstrated method for editing human cells. The team is still testing related proteins to find versions that might work beyond bacteria.
Gene-editing methods that change one DNA base or a few bases can address some errors. Inserting a much larger stretch of DNA at a precise location is harder, and placement at the wrong site can create complications. Cornell microbiology professor Joe Peters, the studyās senior author, compared the difference to replacing a sentence or paragraph rather than a single letter or word.
Two bacterial components work together
The researchers engineered a non-CRISPR system by combining bacterial components that do not naturally occur together. One protein, TldR, uses an RNA guide to find the intended location in a genome. Another, TniQ, helps connect the machinery that inserts the DNA payload in one orientation and at that position, according to Cornell.
The source components are related to the evolutionary origins of CRISPR-Cas systems, but the engineered combination is a separate approach. Cornell said a related set of experiments also used an existing CRISPR-Cas system to improve the efficiency and accuracy of placing large DNA segments.
The group has applied for a patent on the RNA-guided transposition tool. It is examining a broader family of proteins related to TldR for other candidates that could function in human or plant cells, but the published work establishes the engineered system in bacteria only.
Size could affect delivery
The new tool is smaller than many CRISPR-Cas systems, Cornell said. That matters because the viruses often used to deliver gene-editing machinery have limited space for DNA cargo, and editing systems derived from bacteria may need additional components to work in plant or human cells.
Smaller size could leave more room for those modifications, Peters said. Whether the approach can be delivered safely or edit DNA accurately in other organisms remains to be shown.
Former Cornell graduate student Richard Schargel and graduate student Laura Chacon Machado were co-first authors. Alba GuarnƩ, a McGill University biochemistry professor, was also a co-author. The National Institutes of Health, Canadian Institutes of Health Research and National Science Foundation funded the study.
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