In a remarkable advancement at the intersection of biotechnology and medical imaging, researchers have unveiled groundbreaking fluorescent proteins capable of emitting light in the near-infrared (NIR) and short-wave infrared (SWIR) spectra. This leap forward promises to revolutionize our ability to visualize intricate biological processes deep within living tissues, surpassing the limitations imposed by conventional visible light imaging. Led by Professor Oliver Bruns at the National Center for Tumor Diseases (NCT/UCC) Dresden, this research harnesses cutting-edge computational protein design to create entirely novel fluorescent proteins, artificially engineered to fluoresce in spectral regions previously inaccessible through natural biological molecules.
Traditional fluorescent proteins, such as the ubiquitous green fluorescent protein (GFP), have transformed biological imaging but remain constrained by their emission in the visible light spectrum. Their use is often hampered by limited tissue penetration and significant background autofluorescence, which diminish image clarity and depth. The NIR and SWIR ranges, by contrast, offer superior tissue penetration capabilities and reduced scattering, generating cleaner signals from deeper within biological specimens. However, until now, fluorescent proteins with activity in these wavelengths had not been observed or crafted from scratch.
The team spearheaded by Bruns, who was honored in 2024 with the Helmholtz High Impact Award for his pioneering contributions to SWIR imaging, devised fluorescent proteins through de novo protein design—a sophisticated method that uses computational tools and molecular modeling to construct proteins with predefined properties absent in nature. By integrating these tailored proteins with precisely synthesized fluorescent dyes, they successfully engineered proteins exhibiting strong fluorescence in long-wavelength domains, with one protein demonstrating significant brightness in the far-red spectrum and the other extending fluorescence comfortably into the SWIR window.
This approach marks a pivotal breakthrough in synthetic biology and optical imaging, as elucidated by Bernardo Arús, a research associate in Bruns’s group. The ability to computationally design proteins that can activate fluorescence at these wavelengths not only broadens the functional landscape of biomolecules but also opens new frontiers in medical diagnostics. These innovations have been validated through rigorous in vitro experiments in cell cultures and in vivo studies in animal models, showcasing the proteins’ capacity for high-sensitivity visualization of biological structures deep within tissues.
The implications for disease monitoring and surgical procedures are substantial. Leveraging SWIR fluorescence-activating proteins could enable clinicians to detect minute clusters of cancer cells at tumor margins and lymph nodes during surgery, enhancing the precision of tumor resections and improving patient outcomes. Moreover, this technology could illuminate complex biological phenomena in fundamental research, deepening our understanding of physiological and pathological processes without invasive interventions.
Central to the team’s success has been the fusion of computational biology with chemical synthesis of custom dyes, which work synergistically with the engineered proteins to achieve the desired spectral emission. This multidisciplinary strategy underscores the potential of AI-guided design in developing next-generation biomolecular tools tailored to specific scientific and clinical challenges. As Bruns points out, such advancements herald a new era where biological functions once exclusive to nature can be deliberately crafted with digital precision and chemical ingenuity.
The collaborative nature of this project reflects its global significance, involving esteemed institutions spanning North America, Europe, and Asia. Contributions from the Institute for Protein Design at the University of Washington, Howard Hughes Medical Institute, and the National Institute of Biological Sciences in China, alongside prominent European research centers including the German Cancer Research Center (DKFZ), TUD Dresden University of Technology, Helmholtz centers in Dresden and Munich, and the MRC Laboratory of Molecular Biology in the UK, attest to the universal interest and impact of these findings.
At its core, the technology exploits the unique interaction between SWIR light and biological tissues. SWIR wavelengths penetrate more deeply with less scattering and absorption by endogenous chromophores, mitigating interference caused by autofluorescence and thereby enhancing the signal-to-noise ratio in optical imaging. These properties position SWIR imaging coupled with fluorescent proteins as a transformative approach to visualize cellular and molecular phenomena previously obscured in clinical and laboratory environments.
Looking forward, the engineered NIR and SWIR fluorescent proteins could be further refined and adapted to tag various biomolecules, enabling multiplexed imaging and real-time monitoring of molecular dynamics in complex biological systems. This versatility could expand their utility beyond oncology to diverse fields such as neurology, immunology, and developmental biology, where the ability to peer deep inside living organisms can unlock vital insights.
The study is published in the Journal of the American Chemical Society, reflecting its high scientific rigor and innovation. The research not only advances our technical capabilities but also epitomizes the convergence of biology, chemistry, and computational sciences in addressing challenging medical problems. It highlights the promise of modern protein engineering to create custom biological tools with unprecedented functionalities, fundamentally reshaping our approach to biomedical imaging.
As the imaging technology continues to evolve, the potential to integrate these novel proteins with next-generation cameras and imaging systems could yield devices capable of capturing detailed biological landscapes with exceptional clarity and depth. This could facilitate minimally invasive diagnostics, more effective therapeutic monitoring, and personalized treatment strategies tailored to the unique biological signatures within each patient.
In summary, the development of these de novo designed NIR and SWIR fluorescent proteins represents a paradigm shift in biological imaging, enabling visualization beyond the visible spectrum and pushing the boundaries of what is possible in live-cell and deep-tissue investigation. Prof. Oliver Bruns and his international team’s innovative approach underscores a new horizon where artificial proteins designed via computational methods will become essential tools in medical science and research.
Subject of Research: De novo design of fluorescent proteins emitting in the near-infrared and short-wave infrared spectra for advanced biomedical imaging
Article Title: De Novo Design of Near-Infrared Fluorescence-Activating Proteins
News Publication Date: 2-Jun-2026
Web References:
DOI: 10.1021/jacs.5c19594
Keywords
Fluorescent proteins, Near-infrared fluorescence, Short-wave infrared imaging, De novo protein design, Computational protein engineering, Biomedical imaging, Tumor detection, Synthetic biology, Fluorescence dyes, Optical imaging, Deep tissue visualization, Cancer diagnostics
