University of Zurich scientists have developed an enhanced version of TnpB, a small protein found in bacteria and archaea, for more efficient gene editing. This advancement, published in Nature Methods, builds on the discovery that TnpB is an evolutionary precursor to the larger Cas proteins used in CRISPR systems.
The team engineered TnpB from Deinococcus radiodurans, a highly resilient bacterium. The team modified TnpB to improve its nuclear localization and broaden its target range, resulting in a 4.4-fold increase in DNA modification efficiency.
To optimize TnpB's performance, the scientists tested it on over 10,000 different target sites. They developed an AI model to predict TnpB editing efficiencies, achieving up to 75.3% efficiency in mouse livers and 65.9% in mouse brains.
Search Antibodies Search Now Use our Antibody Search Tool to find the right antibody for your research. Filter
by Type, Application, Reactivity, Host, Clonality, Conjugate/Tag, and Isotype.
The compact size of TnpB allows for efficient delivery using a single Adeno-associated viral vector, unlike larger CRISPR-Cas9 systems that require multiple vectors. This feature could make TnpB more suitable for clinical applications.
In a proof-of-concept study, the researchers used TnpB to edit a gene regulating cholesterol levels in mice with familial hypercholesterolemia, reducing cholesterol by nearly 80%.