Biomolecular regulation with interlocked cyclic oligonucleotides

Introduction

Developing molecules that display protein-like functions and efficiently operate in complex biological environments, e.g. cells, is a grand challenge in chemistry. The aim of BioRIcON is to develop a novel class of biohybrid interlocked molecules (BIMs) that mirrors the function of proteins and enables precise biomolecular regulation.

Current Challenges

Despite the advances of interlocked molecules, often compared to biological motors, their use in cellular or in vivo settings pales compared to their natural counterparts. BioRIcON comprises an entirely new concept in artificial biology and biomolecular control by yielding BIMs that contain dynamic components ultimately designed to efficiently actuate in cells with high spatio-temporal resolution.

Methodology

I will develop molecular switches and motors using small cyclic oligonucleotides (cONs) that will be mechanically bound – like links in a chain - to other biomolecules to regulate their function. The resulting BIMs merge the best of two worlds:

1. The programmability and biocompatibility features of oligonucleotides.
2. The robustness and scalable production of synthetic mechanically interlocked systems.

Goals

The goals of BioRIcON include:

1. Developing BIM-based shuttles and motors that can operate effectively in biological environments, integrate, and react to cellular cues and signaling.
2. Exploring mechanical interlocking for reversible molecular display and protection against degradation.
3. Implementing BIMs in biomolecular regulation, focused on reversible oligonucleotide-based therapies.

Impact

BioRIcON will significantly advance the toolbox of biomimetic systems and enable their integration in processes such as gene regulation and protein expression. BIMs use mechanical interlocking to reversibly protect and control biomolecular function in an adaptive manner, with a focus on RNA regulation which will help unravel the mechanisms of fundamental biological processes and hold enormous innovative potential in biosensing and biomedicine.