Medical Design Briefs - August 2023 - 28

Drug Development
Drug Development
AI Tailors DNA for Future Drug Development
AI " prints " the appropriate DNA sequence.
W
ith the help of an AI, researchers have succeeded in
designing synthetic DNA that controls the cells' protein
production. The technology can contribute to
the development and production of vaccines, drugs for severe
diseases, as well as alternative food proteins much faster and at
significantly lower costs than today.
How our genes are expressed is a process that is fundamental
to the functionality of cells in all living organisms. Simply put,
the genetic code in DNA is transcribed to the molecule messenger
RNA (mRNA), which tells the cell's factory which protein
to produce and in which quantities.
Researchers have put a lot of effort into trying to control
gene expression because it can, among other things, contribute
to the development of protein-based drugs. A recent example
is the mRNA vaccine against COVID-19, which instructed
the body's cells to produce the same protein found on the surface
of the coronavirus. The body's immune system could then
learn to form antibodies against the virus. Likewise, it is possible
to teach the body's immune system to defeat cancer cells or
other complex diseases if one understands the genetic code
behind the production of specific proteins.
DNA Controls the Quantity of a Specific Protein
Most of today's new drugs are protein-based, but the techniques
for producing them are both expensive and slow, because
it is difficult to control how the DNA is expressed. Last
year, a research group at Chalmers University of Technology,
led by Aleksej Zelezniak, associate professor of systems biology,
took an important step in understanding and controlling
how much of a protein is made from a certain DNA
sequence.
" First it was about being able to fully 'read' the DNA molecule's
instructions. Now we have succeeded in designing our
own DNA that contains the exact instructions to control the
quantity of a specific protein, " says Zelezniak about the research
group's latest important breakthrough.
DNA Molecules Made-to-Order
The principle behind the new method is similar to when an
AI generates faces that look like real people. By learning what
a large selection of faces looks like, the AI can then create
completely new but natural-looking faces. It is then easy to
modify a face by, for example, saying that it should look older,
or have a different hairstyle.
On the other hand, programming a believable face from
scratch, without the use of AI, would have been much more
difficult and time-consuming. Similarly, the researchers' AI has
been taught the structure and regulatory code of DNA. The AI
then designs synthetic DNA, where it is easy to modify its regulatory
information in the desired direction of gene expression.
Simply put, the AI is told how much of a gene is desired and
then 'prints' the appropriate DNA sequence.
" DNA is an incredibly long and complex molecule. It is thus
experimentally extremely challenging to make changes to it by
28
Read the study: Controlling gene
expression with deep generative design
of regulatory DNA.
iteratively reading and changing it, then reading and changing
it again. This way it takes years of research to find something
that works. Instead, it is much more effective to let an AI learn
the principles of navigating DNA. What otherwise takes years is
now shortened to weeks or days, " says first author Jan Zrimec, a
research associate at the National Institute of Biology in Slovenia
and past postdoc in Zelezniak's group.
Efficient Development of Proteins
The researchers have developed their method in the yeast
Saccharomyces cerevisiae, whose cells resemble mammalian cells.
The next step is to use human cells. The researchers have
hopes that their progress will have an impact on the development
of new as well as existing drugs.
" Protein-based drugs for complex diseases or alternative sustainable
food proteins can take many years and can be extremely
expensive to develop. Some are so expensive that it is impossible
to obtain a return on investment, making them
eco nomically nonviable. With our technology, it is possible to
develop and manufacture proteins much more efficiently so
that they can be marketed, " says Zelezniak.
The authors of the study are Jan Zrimec, Xiaozhi Fu, Azam
Sheikh Muhammad, Christos Skrekas, Vykintas Jauniskis, Nora
K. Speicher, Christoph S. Börlin, Vilhelm Verendel, Morteza
Haghir Chehreghani, Devdatt Dubhashi, Verena Siewers, Florian
David, Jens Nielsen and Aleksej Zelezniak. The researchers
are active at Chalmers University of Technology, National Institute
of Biology, Slovenia; Biomatter Designs, Lithuania; Institute
of Biotechnology, Lithuania; BioInnovation Institute, Denmark;
King's College London, UK.
This article was written by Karin Wik, Chalmers University of
Technology. For more information, contact Aleksej Zelezniak,
Associate Professor, Systems Biology, Life Sciences, at aleksej.
zelezniak@chalmers.se or visit www.chalmers.se.
Researchers have succeeded in designing synthetic DNA that controls the cells' protein
production. (Credit: Chalmers University)
www.medicaldesignbriefs.com
Medical Design Briefs, August 2023
http://www.chalmers.se http://www.medicaldesignbriefs.com
Medical Design Briefs - August 2023

Table of Contents for the Digital Edition of Medical Design Briefs - August 2023
