Next-generation RNA therapy: a way to selectively turn on gene therapy in human cells

A new ribonucleic acid can be used to trigger the production of therapeutic proteins to treat cancer or other diseases

Researchers at the Massachusetts Institute of Technology (MIT) and Harvard University (Harvard University) have devised a method that can selectively initiate gene therapy on 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

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

"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

The research was published in the journal Nature Biotechnology on October 28, 2021.

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
.
As an example, they showed that they can detect the expression of heat shock proteins, which are produced when cells are exposed to high temperatures
.

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
.
This targeting can allow researchers to develop a treatment method that triggers cell death when a cancerous protein is detected in a cell
.

Mao said: "Our idea is that we can target any unique RNA marker and provide treatment
.
This may be a way to limit the expression of biomolecules to target cells or tissues
.
"

This new technology represents "a huge leap forward in the concept of controlling and programming the behavior of mammalian cells," said Martin Fusenger, professor of biotechnology and bioengineering at ETH Zurich, who was not involved in the research
.
"This new technology sets new standards for human cells to perceive and respond to viruses such as Zika virus and SARS-CoV-2
.
"

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