Year: 2025
Type: article
Abstract: Directed evolution is a process of mutation and artificial selection to breed biomolecules with new or improved activity. Directed evolution platforms are primarily prokaryotic or yeast-based, and stable mammalian systems have been challenging to establish and apply. To this end, we develop PROTein Evolution Using Selection (PROTEUS), a platform that uses chimeric virus-like vesicles to enable extended mammalian directed evolution campaigns without loss of system integrity. This platform is stable and can generate sufficient diversity for directed evolution in mammalian systems. Using PROTEUS, we alter the doxycycline responsiveness of tetracycline-controlled transactivators, generating a more sensitive TetON-4G tool for gene regulation with mammalian-specific adaptations. PROTEUS is also compatible with intracellular nanobody evolution, and we use it to evolve a DNA damage-responsive anti-p53 nanobody. Overall, PROTEUS is an efficient and stable platform to direct evolution of biomolecules within mammalian cells.
Source: Nature Communications
Institutions: The University of Sydney, Centenary Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Histone methyltransferases control pain perception, Defining the cellular and molecular factors that control central inhibition and neuropathic pain, Systematic multidisciplinary approach to define impacts, molecular mechanisms, and ways to treat PFAS exposure., Transcriptional regulation of nociceptor function and extreme genetic pain disease
OpenAlex ID: W4410139679