Department of CBE - Sonopharmacology and Sonogenetics: Activation of Drugs, Proteins and Nucleic Acids by Ultrasound
The field of optogenetics has enabled the fundamental understanding of neural circuits and disorders.[1,2] However, current optogenetic techniques require invasive surgical procedures to deliver light to target cells due to the low penetration depth of light into tissue. Therefore, ultrasound (US) was used as alternative trigger since US can deeply penetrate tissue with high spatiotemporal control. Our group develops general molecular technologies based on nucleic acid aptamers and mechanochemistry to control the activity of proteins and drugs by US.[3,4,5,6] Therefore, we produce high molecular weight polynucleic acids by rolling circle amplification or transcription that encode multiple aptamer binding sites for proteins or drugs. Once these loaded nucleic acid carriers are subjected to ultrasonication, covalent and non-covalent bond cleavage occurs by collapse of US-induced cavitation bubbles leading to activation of the cargoes. Similarly, we liberate small bioactive trigger molecules by US that initiate gene knock-down involving aptazymes encoded on mRNA. A particular emphasis is paid to reducing US energies to make these sonogenetic and sonopharmacological systems compatible with living matter.[3,6,7] In this context, oligonucleotides were released from high molar mass nucleic acid carriers allowing to stimulate immune reactions site specifically in the liver of mice by imaging US.[7] A second platform technology for low-intensity US activation is mechanophore-incorporated microbubbles that also allow the spatiotemporally controlled release of bioactives.[8]
References
- W. Haubensak, P. S. Kunwar, S. Ciocchi, J. Biag, H.-W. Dong, K. Deisseroth, E. M. Callaway, M. S. Fanselow, A. Lüthi, A. J. Anderson, Nature 468, 270 (2010).
- A. V. Kravitz, B. S. Freeze, P. R. Parker, K. Kay, M. T. Thwin, K. Deisseroth, A. C. Kreitzer, Nature 466, 622 (2010).
- P. Zhao, S. Huo, J. Fan, J. Chen, F. Kiessling, A. J. Boersma, R. Göstl, A. Herrmann, Angew. Chem. Int. Ed. 60, 14707 (2021).
- S. Huo, P. Zhao, Z. Shi, M. Zou, X. Yang, E. M. Warszawik, M. Loznik, R. Göstl, A. Herrmann, Nat. Chem. 13, 131 (2021).
- D. Yildiz, R. Göstl, A. Herrmann, Chem. Sci. 13, 13708 (2022).
- J. Hahmann, A. Ishaqat, T. Lammers, A. Herrmann, Angew. Chem. Int. Ed. 63, e202317112 (2024).
- A. Ishaqat, J. Hahmann, C. Lin, X. Zhang, C. He, W. H. Rath, P. Habib, S. E. M. Sahnoun, K. Rahimi, R. Vinokur, F. M. Mottaghy, R. Göstl, M. Bartneck, A. Herrmann, Adv. Mat. 2403752 (2024).
- M. Xuan, J. Fan, V. N. Khiêm, M. Zou, K.‐O. Brenske, A. Mourran, R. Vinokur, L. Zheng, M. Itskov, R. Göstl, A. Herrmann, Adv. Mat. 35, 2305130 (2023).
Andreas Herrmann studied chemistry at the University of Mainz (Germany). From 1997 to 2000 he pursued his graduate studies at the Max Planck Institute for Polymer Research in Mainz, Germany, in the group of Prof. Klaus Müllen. Then he worked as a consultant for Roland Berger Management Consultants in Munich (2001). In the years 2002 and 2003, he returned to academia as a postdoctoral fellow working on protein engineering with Prof. Don Hilvert at the Swiss Federal Institute of Technology, Zurich. In 2004, he was appointed as a head of a junior research group at the Max Planck Institute for Polymer Research. From 2007 to 2017 he held a position as full professor at the Zernike Institute for Advanced Materials at the University of Groningen, the Netherlands, where he headed the chair for Polymer Chemistry and Bioengineering. Since June 2017, he is scientific board member of the DWI – Leibniz Institute for Interactive Materials in Aachen, Germany, and fills a position as full professor at RWTH Aachen University for Macromolecular Materials and Systems. In 2018, he became vice-director of the DWI – Leibniz Institute and director in 2023.