RNA Technology Enables Precise Control of Gene Networks

Scientists have created a smart RNA that can control networks in response to different signals by converting guide RNAs, which normally direct enzymes. The scholarly community is paying close attention to this ground-breaking study.

A research team led by Professor Jongmin Kim and comprised of Ph.D. candidates Hansol Kang and Dongwon Park from the Department of Life Sciences at POSTECH has created a multi-signal processing guide RNA.

It is possible to program this guide RNA to rationally control gene expression. The international journal of molecular biology and biochemistry, Nucleic Acids Research, recently published the study.

Often called “gene scissors,” the CRISPR/Cas system allows the editing of gene sequences to add or remove biological functions. A guide RNA, which tells the enzyme to change the gene sequence at a particular location, is essential to this technology, which is used to engineer crops and treat genetic diseases genetically.

While research into guide RNAs that react to biological signals has increased due to advancements in RNA engineering, precisely controlling gene networks to react to multiple signals has proven difficult.

To circumvent these restrictions, the researchers in this study combined biocomputing with the CRISPR/Cas system. Biocomputing technology links biological elements, such as electronic circuits, to control cellular and organismal functions.

One of the basic representations of input-output relationships in digital signal operations, a Boolean logic gate, is analogous to the guide RNA gene circuit that the researchers developed. It is capable of making decisions based on inputs.

To process different signals and complex inputs, the team combined multiple logic gates and successfully controlled key genes involved in E. coli metabolism and cell division. They used this circuit to regulate the proper level of metabolic flows and cell morphology.

This work is important because it combines current technologies and systems to precisely control gene networks, allowing an organism to process, integrate, and respond to various signals. This is more than just guide RNAs pointing enzymes in the right direction.

The research could enable the precise design of gene therapies based on biological signals within complex genetic circuits involved in disease. RNA molecular engineering allows for the simplicity of software-based structure design which will significantly advance the development of personalized treatments for cancer, genetic disorders, metabolic diseases, and more.”

Jongmin Kim, Professor, Pohang University of Science and Technology 

Source:
Journal reference:

Kang, H., et al. (2024) Logical regulation of endogenous gene expression using programmable, multi-input processing CRISPR guide RNAs. Nucleic Acids Research. doi.org/10.1093/nar/gkae549

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