Nature Biotechnology: A new way to selectively turn on RNA therapy in human cells

Researchers at the Massachusetts Institute of Technology (MIT) and Harvard University (Harvard University) have devised a method that can selectively initiate gene therapy for target cells, including human cells

Since the expression of transgenes in the wrong cells may have negative or even dangerous effects, researchers hope to find a way to reduce the off-target effects of gene therapy

Researchers have found a way to produce genetically modified genes only after "reading" specific RNA sequences in cells, thereby developing a technology that can fine-tune gene therapy, with applications ranging from regenerative medicine to cancer treatment

"This brings new control circuits to the emerging field of RNA therapy and opens up the next generation of RNA therapies that can be initiated only in a cell or tissue specific way," the Massachusetts Institute of Technology Institute of Medical Engineering and Science (IMES) and Said James Collins, professor of medical engineering and science in the Department of Bioengineering and senior author of the study

Researchers say that this highly targeted approach is based on genetic elements that viruses use to control gene translation in host cells and can help avoid some of the side effects of treatments that affect the entire body

Evan Zhao, a researcher at the Wyss Institute for biological Inspired Engineering at Harvard University, and An Ji, a postdoctoral fellow at the Massachusetts Institute of Technology (MIT) and a technical researcher at the Wyss Institute Angelo Mao is the lead author of the study, which was published today in the journal Nature Biotechnology

RNA detection

A messenger RNA (mRNA) molecule is a sequence of RNA that encodes the instructions for building a specific protein

The foothold of RNA also contains a sequence that can be combined with a different mRNA sequence as a trigger

In this new study, the researchers began to try to create a similar system that can be used in eukaryotic (non-bacterial) cells, including human cells

Since gene translation in eukaryotic cells is more complicated, the genetic components they use in bacteria cannot be introduced into human cells

"These are complex folds of RNA.

The researchers started with IRES naturally produced in different types of viruses and designed them to contain a sequence that binds to the triggering mRNA

Targeted treatment

Researchers use this technology to develop footpoints that can detect various triggers in human and yeast cells

They also designed foothold molecules that can detect mRNAs for proteins naturally produced in human cells, which help reveal cell states, such as stress

Finally, the researchers stated that they can identify cancer cells by detecting the engineered toe of tyrosinase mRNA, an enzyme that produces excess melanin in melanoma cells

Mao said: "Our idea is to target any unique RNA markers and provide treatment

All the research done in this article was conducted on cells cultured in a laboratory dish
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Researchers are currently studying delivery strategies to enable the RNA components in the system to reach target cells in animal models
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Article title

RNA-responsive elements for eukaryotic translational control