Remote controlling biological systems by sonopharmacology and sonogenetics

Introduction

To date, light has been employed as a widespread trigger to achieve control over the activity of drugs and protein function, establishing the fields of photopharmacology and optogenetics, respectively. Both techniques led to promising new therapies, the elucidation of brain function, or understanding of neural disorders.

Limitations of Current Techniques

However, serious limitations resulting from the low penetration depth of light into tissues are severely hampering progress in these fields. In contrast to photons, ultrasound deeply penetrates tissue and can be applied with sub-millimeter resolution. Consequently, it has been widely established in the clinic over many decades for therapy and diagnostics.

Project Overview

In this ERC Advanced Grant, I will develop a radically new approach to control the activity of drugs, proteins, and genes by biocompatible ultrasound. Polynucleic acid carriers, which can bind a wide variety of bioactive payloads, will be designed to be sensitive to different ultrasound sources. These sources can be applied in clinical settings and do not harm cells or tissues.

Mechanism of Action

Upon ultrasound irradiation, these carriers liberate their bioactive payloads by mechanochemical principles to switch on drugs and control cellular functions.

Research Objectives

To achieve this aim, I will:

1. Investigate the effect of ultrasound (US) on nucleic acid architectures.
2. Study the loading of polynucleic acids with different payloads and their release by US.
3. Develop a technology platform to activate small molecule drugs, proteins, and oligonucleotides.
4. Showcase the huge potential of these technologies for cancer immunotherapy, diabetes research, and tissue engineering.

Expected Outcomes

This project will boost sonopharmacology and sonogenetics. Its outcomes will enable spatiotemporal control of drug action to minimize side effects in pharmacotherapy, such as cancer. The remote-controlled orchestration of protein and gene function by US will strongly advance medicine and the life sciences by answering fundamental questions in these fields.