Local control of Cre-regulated genetic modeling in vivo using wireless implantable optoelectronics
Effective modeling of chronic human diseases in vivo requires precise spatiotemporal regulation of molecular processes at defined tissue locations. Optogenetic and optoelectronic tools can provide such control but targeting internal organs such as the lungs remain challenging. To address this, we developed E-LightR-Cre recombinase, enabling precise, spatially restricted gene activation with no dark-state activity and robust blue light responsiveness. To achieve local activation of E-LightR-Cre in specific organ sites, we engineered wireless, fully implantable optoelectronic devices enabling focal illumination of murine lungs with no discernible organ damage. The size of the activated area is controlled by modulating light intensity and duration. Using implanted optoelectronic devices, we activated E-LightR-Cre in a selected area of mouse lungs and achieved local regulation of targeted genes. Light-regulated expression of the oncogenic KRas-G12D mutant in mouse lungs induced local formation of oncogenic lesions. These results show that our protein engineering and adaptable optoelectronic approaches enable facile application of optogenetic tools for locally controlled disease modeling in vivo.
Authors
- John A. Rogers (ORCID: https://orcid.org/0000-0002-3830-5980)
- Yonggang Y. Huang (ORCID: https://orcid.org/0000-0002-0483-8359)
- Andrei V. Karginov (ORCID: https://orcid.org/0000-0003-2370-6383)
- Cameron H. Good (ORCID: https://orcid.org/0000-0002-0183-4854)
- Raudel O. Avila (ORCID: https://orcid.org/0009-0005-0092-5307)
- Péter T. Tóth (ORCID: https://orcid.org/0000-0003-2168-0124)
- Chad R. Haney (ORCID: https://orcid.org/0000-0001-5981-2925)
- Haohui Zhang (ORCID: https://orcid.org/0000-0001-8432-3672)
- Y.J. Kim (ORCID: https://orcid.org/0009-0000-0553-2995)
- Yuanting Wei (ORCID: https://orcid.org/0000-0001-5779-5332)
- Ameen Abdulla Salahudeen (ORCID: https://orcid.org/0000-0001-9037-3481)
- Huong Huynh (ORCID: https://orcid.org/0009-0002-6022-1377)
- Anthony R. Banks (ORCID: https://orcid.org/0000-0002-0509-0370)
- Seung Young Lee (ORCID: https://orcid.org/0000-0003-1349-3759)
- Shaluah Vijeth (ORCID: https://orcid.org/0000-0003-0903-6651)
- Olga A. Karginova (ORCID: https://orcid.org/0009-0006-0250-2030)
- Jacob Matsche (ORCID: https://orcid.org/0000-0003-4743-0297)
- Jalees Rehman (ORCID: https://orcid.org/0000-0002-2787-9292)
- Yuru Liu (ORCID: https://orcid.org/0000-0001-9275-9513)
- Yaner Chen
- Varsha Sreekanth (ORCID: https://orcid.org/0000-0001-7191-3083)
- Minsung Kim (ORCID: https://orcid.org/0000-0003-2468-2061)
- Shupeng Li (ORCID: https://orcid.org/0000-0002-8723-9369)
- Kento Yamagishi (ORCID: https://orcid.org/0000-0002-2209-7910)
- Min‐Kyu Lee (ORCID: https://orcid.org/0000-0002-8770-585X)
- Young-Mee Kim (ORCID: https://orcid.org/0000-0001-6616-2393)
- Jiheon Kang (ORCID: https://orcid.org/0009-0009-4390-787X)
- Odile David (ORCID: https://orcid.org/0000-0002-6539-2573)
- Trisha Bansal (ORCID: https://orcid.org/0000-0002-7047-4389)
- Farah Yousef
- Dane Hintermueller
- Sophianne Loh (ORCID: https://orcid.org/0009-0006-6838-7549)
- Sachin Clark (ORCID: https://orcid.org/0000-0003-1349-3759)
- Kaiqing Zhang
- Kaitlyn Mowry (ORCID: https://orcid.org/0009-0009-1096-1976)
- Courtney Coleman (ORCID: https://orcid.org/0009-0009-3061-3389)
Institutions
- Northwestern University (US)
- Shirley Ryan AbilityLab (US)
- Illinois College (US)
- Nanyang Technological University (SG)
- University of Cambridge (GB)
- University of Illinois Chicago (US)
- University of Illinois Hospital & Health Sciences System (US)
- Chemistry of Life Processes Institute (US)
- Rice University (US)
- The University of Tokyo (JP)
Publication Details
- Journal
- Science Advances
- Published
- 2026-10-14
- DOI
- https://doi.org/10.1126/sciadv.aed1014
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- National Institutes of Health
- International Institute for Nanotechnology, Northwestern University
- National Cancer Institute
- National Institute of General Medical Sciences