Penn Researcher George M. Burslem Co-Authors Breakthrough Science Study Introducing a New Method for Editing Proteins Inside Living Cells

George M. Burslem, assistant professor of Biochemistry and Biophysics in the Perelman School of Medicine, has co-authored a landmark study published in Science that introduces a transformative method for editing the primary sequence of proteins inside living mammalian cells. The article, “Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins,” presents a platform that allows researchers to install new amino acids, labels, and functional groups directly into endogenous proteins with unprecedented precision and temporal control

Burslem’s laboratory (https://www.burslemlab.com/) focuses on developing chemical strategies to control protein fate, and this new technology significantly expands the toolkit available for studying protein behavior in real time. As outlined in the article summary on page 1, the method leverages tandem split inteins, genetic code expansion, and genome editing to enable rapid, site-specific modification of native proteins—often within minutes and without disrupting their function

Experimental panels throughout the study—such as the rapid calnexin editing shown on page 2 and the successful editing of β-actin, Chk1, and c-Myc on pages 5–6 demonstrate that the technology performs with high specificity across diverse protein classes. Unlike conventional protein tags or antibody-based approaches, which can be bulky or incompatible with live-cell imaging, this method allows fluorophores, biotin, and other functional groups to be integrated directly at endogenous expression levels.

The Science publication also underscores the vitality of Penn’s research ecosystem. The collaboration between the Burslem and Shalem laboratories reflects the University’s strength in chemical biology, genetics, cellular engineering, and translational discovery, fields that intersect to accelerate technological innovation. Their combined work illustrates how Penn’s interdisciplinary framework supports breakthroughs that reshape experimental possibilities across biomedical research.

As described in the discussion section on page 9, the authors anticipate that this protein-editing platform will “enable unprecedented access to proteins, both exogenous and endogenous, in situ in mammalian cells,” offering new opportunities for imaging, mechanistic studies, and the development of next-generation therapeutic strategies.

The full Science article is available at: https://doi.org/10.1126/science.adr5499.