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Researchers develop a method for specifically engaging RNA treatments in human cells

Nov, 2021

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Since transgenes do have severe and even deadly consequences when expressed in the incorrect cells, the researchers aimed to find a technique to decrease off-target effects from genetic testing. Analyzing the RNA sequences in cells, which range from tissue to tissue, is one method of recognizing different cell types.

Harvard and MIT University researchers have devised a method for selectively activating gene treatments in target cells, even human cells. Their method detects specific messenger RNA sequences in cells, which then causes a transgenic, or artificial gene, to produce a specific protein. The researchers created a system that might fine-tune gene treatments in various applications from regenerative medicine to treating cancer by discovering a mechanism to manufacture transgene only after reading specific RNA sequences inside cells. For instance, by engineering their system to determine cancerous cells and release a harmful protein specifically within these cells, researchers may develop new medicines to eradicate tumors.

According to the researchers, this highly customized method, which is based on a genetic element utilized by viruses to regulate gene translations in host cells, could assist to prevent some of the negative effects of medicines that affect the entire body. The researchers started with naturally available IRES from several types of viruses and modified them to add a sequence that attaches to a trigger mRNA. When the designed IRES is introduced before an output transgene in a human cell, it prevents translation of that gene unless the triggering mRNA is recognized within the cell. The trigger restores the IRES, allowing the gene to be processed in protein. Initially, the team demonstrated the ability to detect mRNA expressing viral genes from the Zika virus and the SARS virus. Developing T cells that recognize and respond to viral mRNA during infection is one such application. The researchers demonstrated the ability to recognize cancerous cells by developing toeholds that detect mRNA for tyrosinase, an enzyme that creates excess melanin in melanoma cells. When cancer proteins are discovered in a cell, this type of targeting could allow researchers to build medicines that induce the synthesis of a protein that causes cell death.

All of the experiments in this work were carried out on cells grown in a lab dish. The researchers are now developing delivery systems that allow the system's RNA components to access target cells in lab animals.

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