Multi-variable control to mitigate loads in CRISPRa networks: Extended Version
Journal:
arXiv
Published Date:
Sep 11, 2024
Abstract
The discovery of CRISPR-mediated gene activation (CRISPRa) has transformed
the way in which we perform genetic screening, bioproduction and therapeutics
through its ability to scale and multiplex. However, the emergence of loads on
the key molecular resources constituting CRISPRa by the orthogonal short RNA
that guide such resources to gene targets, couple theoretically independent
CRISPRa modules. This coupling negates the ability of CRISPRa systems to
concurrently regulate multiple genes independent of one another. In this paper,
we propose to reduce this coupling by mitigating the loads on the molecular
resources that constitute CRISPRa. In particular, we design a multi-variable
controller that makes the concentration of these molecular resources robust to
variations in the level of the short RNA loads. This work serves as a
foundation to design and implement CRISPRa controllers for practical
applications.
