Scientists are using logic gate-based decision-making to create circuits that regulate genes.
Guides usually help tourists with directions, but imagine if they could offer personalized services tailored to individual interests. Recently, researchers have upgraded guide RNAs, which guide enzymes, into smart RNAs capable of controlling networks in response to different signals. This groundbreaking research is gaining significant attention in the academic community.
Professor Jongmin Kim and PhD candidates Hansol Kang and Dongwon Park from the Department of Life Sciences at POSTECH have developed a multi-signal processing guide RNA. This RNA can be programmed to logically regulate gene expression. Their findings were recently published in Nucleic Acids Research, an international journal of molecular biology and biochemistry.
The CRISPR/Cas system, known as “gene scissors,” is a technology that can edit gene sequences to enhance or remove biological functions. At the core of this technology is a guide RNA that directs the enzyme to edit the gene sequence at a specific location. While advancements in RNA engineering have led to research on guide RNAs that respond to biological signals, achieving precise control of gene networks to respond to multiple signals has been a challenge.
In this study, the team combined the CRISPR/Cas system with biocomputing to overcome these challenges. Biocomputing is a technology that links biological components like electronic circuits to program cellular and organismal activities. The researchers developed a guide RNA gene circuit capable of decision-making based on inputs, similar to a Boolean logic gate, a fundamental concept in digitized signal operations representing input-output relationships.
The team successfully managed essential genes involved in E. coli metabolism and cell division, showcasing the ability to combine multiple logic gates for processing various signals and complex inputs. They used this circuit to control cell shape and metabolic processes effectively.
This study is significant because it merges existing systems and technologies to precisely regulate gene networks, enabling the processing, integration, and response to diverse signals within an organism. It expands the role of guide RNAs beyond directing enzymes to specific locations.
Professor Jongmin Kim of POSTECH mentioned, “The research could lead to the precise design of gene therapies based on biological signals within complex genetic circuits related to diseases.” He further stated, “RNA molecular engineering simplifies the design of structures similar to software, which will greatly advance the development of personalized treatments for cancer, genetic disorders, metabolic diseases, and more.”
The research was funded by the Ministry of Science and ICT, the National Research Foundation of Korea, and supported by various programs and institutes in Korea.
