Shulou(Shulou.com)11/24 Report--

In the movie Terminator 5 starring Schwarzenegger, human leader John is transformed into a semi-robot. After the transformation, John's actions were controlled by the machine and became a puppet of the machine.

Now, some human life activities can really be controlled from the outside world, such as regulating gene expression with electricity.

Jinbo Huang, a Chinese doctoral student from the Federal Institute of Technology Zurich, and his team have developed a new biological interface. This interface is called DC-Actuated Regulation Technology.

It can stimulate cells with electrical signals that turn on or off the expression of a gene.

The study has now appeared in the journal Nature.

So how does DART achieve gene expression control?

There are many ways in which electrical stimulation can regulate gene expression, and this study is based on transcriptional regulation. In eukaryotic genes, there are special sequences called cis/trans-acting elements. These sequences do not encode proteins but control gene expression.

We know that cells are in an environment where there is a lot of water and chloride ions.

When direct current is applied, chlorine gas and hydrogen gas are produced at the negative and positive levels respectively, and free radicals are also produced. Free radicals interact with substances in cells to produce reactive oxygen species (ROS). Keap1-Nrf2-ARE pathway exists in cells, and Keap1 receptor is sensitive to ROS.

Normally, Keap1 and Nrf2 are bound together, and when ROS levels increase, Keap1 releases Nrf2.

Nrf2 enters the nucleus and binds to ARE, which is a cis-acting element. These include promoters recognized by RNA polymerase. ARE binding to Nrf2 is activated, transcription begins, and downstream genes are expressed. For example, the insulin synthesis gene is one of the "downstream genes" here.

When the electrical stimulus disappeared, ROS levels also decreased, the relevant pathways were closed, gene expression stopped, and the reversibility of the operation was realized.

Or it can be used in type 1 diabetes treatment experiments, where researchers re-secrete insulin in mice with type 1 diabetes. However, this process does not use the mouse's own islet B cells, but human cells.

These include the human embryonic kidney cell line (HEK293) and the human mesenchymal stem cell line (hMSC). HEK293 was used to construct, test and regulate the DART system, while hMSC was the target cell for testing.

Through genetic engineering, the researchers engineered hMSC cell lines that incorporated TERT (hMSC-TERT) to express the insulin gene. This cell line has the characteristics of simultaneous proliferation and differentiation, and is commonly used in gene correlation research. The researchers implanted the cells into the backs of mice and stimulated them with an electric current. As a result, these hMSC cells succeeded in secreting insulin.

The research team applied a 4.5V DC power supply to the mice's backs for 10 seconds a day. Results The insulin content of experimental group was significantly higher than that of control group within four weeks. Blood sugar drops rapidly to near-normal levels within the first two days and remains stable for the next four weeks.

Monitoring of glycosylated hemoglobin (HbA1c) levels in mice also showed that they approached normal levels after 4-6 weeks of electrical stimulation. HbA1c is a measure of overall blood glucose levels over time that rules out chance factors for individual blood glucose values.

These experimental results suggest that the theoretical basis for applying this technology to the treatment of type 1 diabetes exists. The next step was to find the appropriate regulatory parameters and implantation methods for humans.

If it succeeds, and even connects DART to the Internet, remote genetic and cellular therapies may be possible. Of course, treating disease is only one of the potential applications of DART, and there may be many more in the future.

We can look forward to the day DART lands.

Address:

https://www.nature.com/articles/s42255-023-00850-7

Reference link:

https://www.vice.com/en/article/g5yjnx/scientists-control-human-dna-with-electricity-in-leap-forward-study-reports

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