[[link removed]]

SUNDAY SCIENCE: POWERFUL PROTEIN EDITORS OFFER NEW WAYS OF PROBING
LIVING CELLS  
[[link removed]]


 

Asher Mullard
May 1, 2025
Nature [[link removed]]

*
[[link removed]]
*
[[link removed]]
*
*
[[link removed]]

_ Scientists deploy self-splicing protein subunits to insert strange
new additions into target proteins. _

Protein molecules (artist’s illustration) fold into their final
shapes. Newly developed editors can swap bits of a protein for other
molecules and amino acids., Ruslanas Baranauskas/Science Photo Library


 

A powerful technique that directly edits proteins in living cells
promises to help researchers to study proteins in improved ways.

The technique relies on strings of amino acids called inteins, which
can autonomously cut themselves out of proteins. Scientists have now
harnessed inteins to splice chemical groups, unusual amino acids and
even polymers into target proteins, and can observe how such additions
affect a protein’s function and cellular location.

The method was described in a pair of papers in _Science_, one
published today1
[[link removed]] and one
in April2
[[link removed]].

The technique is “a very nice addition to the toolbox”, says Mikko
Taipale, a molecular geneticist at the University of Toronto in
Canada, who was not involved in either study. Just as DNA-editing
CRISPR systems
[[link removed]] have transformed
the ability to manipulate genes, intein editors will provide a better
way to investigate the form, function and localization of proteins,
says Taipale.

But whereas CRISPR is ready for use in living cells
[[link removed]], laboratory
animals and humans, current protein editors require finicky
customization and can be used only in cells. The tools are “good for
very specific questions”, says Taipale.

Intein intel

Inteins were discovered in 1990 in baker’s yeast (_Saccharomyces
cerevisiae_), and thousands of these elements have since been
identified in other single-celled organisms. “We call them Houdini
proteins, because they escape from the bondage of the proteins
they’re embedded in,” says Tom Muir, a chemist at Princeton
University in New Jersey and a co-author of the _Science_ paper
published in April. Although inteins’ biological role remains
unclear, for the most part, researchers have long been trying to
repurpose inteins as protein editors.

Progress has been slow: inteins can be hard to work with and are
inefficient editors. But Muir’s group designed new inteins that
perform better than previously available ones. The paper published
today, by George Burslem at the University of Pennsylvania in
Philadelphia, and his colleagues, describes intein systems that are
easier to produce and use in live cells.

The editors, called protein transposons by Muir’s team, require some
groundwork. Researchers first have to reprogram the DNA code for the
protein of interest. This step adds instructions to encode an
‘acceptor site’ where the edit will be made. The site includes two
intein elements at either end.

The researchers then prepare a ‘donor’ protein carrying the
desired cargo to be spliced into the target protein. The cargo is
bracketed by two more intein elements. When the target protein and the
donor align, the split inteins pair up and self-eject from the target
protein, taking the rest of the acceptor site with them. The cargo
slots itself into the gap.

The process is “cut and paste”, says Burslem.

Quick work

Burslem’s team used the editors to make changes in five different
proteins in live cells. The protein editors needed less than ten
minutes to do their work, Burslem says. Muir’s team used a different
set of editors to tweak three proteins.

“Between the two papers, there’s quite a breadth of different
types of proteins that this has been applied to,” says Muir.

These editors provide a powerful new tool for cell-biology
experiments, he adds. The tools can be used to add markers to
proteins, giving scientists a fresh way to track proteins’ actions
and movements. And the editors can paste in stretches of amino acids
that will redefine where a protein goes in the cell, give it a new
function or force it to interact with another protein of interest.

Because the edits happen so fast, researchers can watch the effects in
real time.

The full potential remains to be seen, adds Taipale. “Smart people
will use these technologies in ways that we aren’t thinking about
now.”

Room for improvement

But the intracellular protein editors also have their limitations.

The two teams made their edits at exposed sites and at flexible
regions of the target proteins. Amino-acid stretches that are buried
deep inside highly structured proteins will be harder to edit.

There are other pragmatic considerations. Because of the need to have
an acceptor site, the tools don’t work on unmodified proteins. And
the most efficient way to get the donor sequence into a live cell is
to zap the cell with electricity — putting animal models largely
beyond the range of these editors for now.

But the technology is likely to improve, says Taipale. “This is the
floor, and it’s only going to get better.”

_doi: [link removed]

References

*
Beyer, J. N. _et
al._ _Science_ [link removed] (2025).

Article [[link removed]] Google Scholar
[[link removed].] 

*
Hua, Y. _et al._ _Science_ 388, 68–74 (2025).

Article [[link removed]] PubMed
[[link removed]] Google
Scholar
[[link removed].] 

_ASHER MULLARD is a freelance science journalist, covering drugs,
clinical trials, biotech, pharma and more. Writes for Nature, The
Lancet, The New Scientist, and others._

_NATURE [[link removed]]—the leading international weekly
journal of science first published in 1869—to selective
subject-specific subscription journals including Nature Genetics
[[link removed]] and Nature Physics
[[link removed]] and broad open-access journals such
as Nature Communications
[[link removed]] and Scientific Reports
[[link removed]], there is a home for your research
within our family of journals. We're committed to providing more
options for authors in the open access arena too. The Communications
journals
[[link removed]],
a group of high-quality, selective, open access multidisciplinary
journals, published their first articles in 2018. Our Nature Reviews
titles showcase authoritative, accessible and significant review
content. High-quality graphics and enhanced content provide context
and explanation, whatever your discipline._

_Every month, nine million people read news, analysis and commentary
on nature.com. We are committed to developing the next generation of
scientists through our backing for the Nature Awards for Mentoring
in Science, the John Maddox Prize for Standing up for Science and the
Nature Research Awards for Inspiring and Innovating Science._

__

Two Theories of Consciousness Faced Off. The Ref Took a Beating.
[[link removed]]
Carl Zimmer
New York Times (Origins)
What makes humans conscious? Scientists disagree, strongly, as one
group of peacemakers discovered the hard way.
April 30, 2025

* Science
[[link removed]]
* biology
[[link removed]]
* chemistry
[[link removed]]
* Medicine
[[link removed]]
* protein
[[link removed]]
* editing
[[link removed]]

*
[[link removed]]
*
[[link removed]]
*
*
[[link removed]]

 

 

 

INTERPRET THE WORLD AND CHANGE IT

 

 

Submit via web
[[link removed]]

Submit via email
Frequently asked questions
[[link removed]]
Manage subscription
[[link removed]]
Visit xxxxxx.org
[[link removed]]

Twitter [[link removed]]

Facebook [[link removed]]

 




[link removed]

To unsubscribe, click the following link:
[link removed]