Emergent interactions due to resource competition in CRISPR-mediated genetic activation circuits
Name
CRISPRa_Competition_Submitted.pdf
Description
Accepted version
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1003.36 KB
Format
Adobe PDF
Checksum (MD5)
4341759d7adf0129f4f5f6a0fe7713bc
Author(s)
Manoj, Krishna
Del Vecchio, Domitilla
Date Issued
December 6, 2022
Publisher
IEEE|2022 IEEE 61st Conference on Decision and Control (CDC)
Citation
Manoj, Krishna and Del Vecchio, Domitilla. 2022. "Emergent interactions due to resource competition in CRISPR-mediated genetic activation circuits."
Version
Author's final manuscript
Abstract
CRISPR-mediated gene regulation has gained considerable attention due to its scalability, allowing to create
increasingly large genetic circuits. Unintended interactions due
to competition for the dCas9 resource among different small
guide RNAs have been characterized extensively for CRISPRmediated repression (CRISPRi). Such an analysis is to a large
extent missing for CRISPR-mediated activation (CRISPRa). In
this paper, we model CRISPRa considering two required shared
resources (dCas9 and an activator protein), and identify the
interaction graphs that emerge through resource competition.
The presence of two shared resources among multiple scaffold
RNAs (scRNA) is responsible for two main phenomena. First,
we mathematically prove the existence of a “self-sequestration”
effect, wherein an scRNA represses its own target gene instead
of activating it, thereby negating the CRISPRa function. Second, we demonstrate that unwanted repression of non-target
genes is substantially stronger when compared to a scenario
with a single resource. These results indicate that new control
approaches to concurrently regulate multiple resources will
be useful for mitigating the undesirable effects of resource
competition in CRISPRa.
Description
2022 IEEE 61st Conference on Decision and Control (CDC) December 6-9, 2022. Cancún, Mexico
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Creative Commons Attribution-Noncommercial-ShareAlike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1109/cdc51059.2022.9993376
