Engineers sharpen gene-editing tools to target cystic fibrosis | Penn Today
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Archived: 2026-04-23 17:14
Engineers sharpen gene-editing tools to target cystic fibrosis | Penn Today
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Engineers at Penn’s
School of Engineering and Applied Science
have collaborated to refine a technology for editing individual genetic “base pairs” to a new level of precision, opening the door to safer, more reliable therapies for a wide range of genetic diseases, and to potential treatments for some cystic fibrosis patients that may yield better outcomes than existing therapies.
View large image
Beyond cystic fibrosis, the refined base editor could help researchers tackle a wide range of genetic diseases caused by single-letter DNA changes.
(Image: Bella Ciervo)
“More than a thousand different genetic mutations can cause cystic fibrosis,” says
Xue “Sherry” Gao
, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and in bioengineering (BE) at Penn Engineering, and co-senior author of a new paper in
Molecular Therapy
describing the advance.
To treat conditions like cystic fibrosis, researchers need to develop a suite of tools, rather than a single therapy. But even when scientists know exactly which DNA letter they want to change, today’s gene-editing technologies can unintentionally alter nearby letters as well, introducing “bystander” mutations that raise safety concerns.
“It’s a bit like editing a document,” says Gao. “We can already identify and replace a particular letter in a specific word. How do we change only that one letter without accidentally altering the letters next to it?”
One common cause of genetic diseases, including cystic fibrosis, is the accidental substitution of one nucleotide base—a single “letter” in the genetic code—for another.
“In some cases, the letter should be a T,” says
Tyler C. Daniel
, a Penn Engineering doctoral candidate in CBE and co-first author of the new paper, referring to thymine, one of the four bases in human DNA, along with adenine (A), guanine (G), and cytosine (C). “Instead, it’s a C, which can impair or completely abolish the function of the gene, leading to disease.”
While it’s already possible to use editors to change the C to a T, including a base-pair editor the same researchers devised in 2020, and even to selectively modify just one of two adjacent Cs, problems arise when multiple pairs of cytosines appear close together, in “CC … CC” patterns, separated by just a few other base pairs.
“The issue is precision,” says Daniel. “How do you restrict the editor so it only modifies the targeted letter C you want and leaves its neighbors alone?”
In order to change letters in DNA, base-pair editors combine two essential functions: one component that locates a specific sequence in the genome and another that modifies DNA. Those two parts are physically connected by a segment of molecules known as the “linker.”
By shortening and stiffening the linker, the team effectively limited the enzyme’s reach. “We essentially tightened the leash to ensure only our target was edited,” says Daniel.
Read more at
Penn Engineering
.
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Ian Scheffler
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Skip to Content
Skip to Content
News from
University of Pennsylvania
Try Advanced Search
Engineers at Penn’s
School of Engineering and Applied Science
have collaborated to refine a technology for editing individual genetic “base pairs” to a new level of precision, opening the door to safer, more reliable therapies for a wide range of genetic diseases, and to potential treatments for some cystic fibrosis patients that may yield better outcomes than existing therapies.
View large image
Beyond cystic fibrosis, the refined base editor could help researchers tackle a wide range of genetic diseases caused by single-letter DNA changes.
(Image: Bella Ciervo)
“More than a thousand different genetic mutations can cause cystic fibrosis,” says
Xue “Sherry” Gao
, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and in bioengineering (BE) at Penn Engineering, and co-senior author of a new paper in
Molecular Therapy
describing the advance.
To treat conditions like cystic fibrosis, researchers need to develop a suite of tools, rather than a single therapy. But even when scientists know exactly which DNA letter they want to change, today’s gene-editing technologies can unintentionally alter nearby letters as well, introducing “bystander” mutations that raise safety concerns.
“It’s a bit like editing a document,” says Gao. “We can already identify and replace a particular letter in a specific word. How do we change only that one letter without accidentally altering the letters next to it?”
One common cause of genetic diseases, including cystic fibrosis, is the accidental substitution of one nucleotide base—a single “letter” in the genetic code—for another.
“In some cases, the letter should be a T,” says
Tyler C. Daniel
, a Penn Engineering doctoral candidate in CBE and co-first author of the new paper, referring to thymine, one of the four bases in human DNA, along with adenine (A), guanine (G), and cytosine (C). “Instead, it’s a C, which can impair or completely abolish the function of the gene, leading to disease.”
While it’s already possible to use editors to change the C to a T, including a base-pair editor the same researchers devised in 2020, and even to selectively modify just one of two adjacent Cs, problems arise when multiple pairs of cytosines appear close together, in “CC … CC” patterns, separated by just a few other base pairs.
“The issue is precision,” says Daniel. “How do you restrict the editor so it only modifies the targeted letter C you want and leaves its neighbors alone?”
In order to change letters in DNA, base-pair editors combine two essential functions: one component that locates a specific sequence in the genome and another that modifies DNA. Those two parts are physically connected by a segment of molecules known as the “linker.”
By shortening and stiffening the linker, the team effectively limited the enzyme’s reach. “We essentially tightened the leash to ensure only our target was edited,” says Daniel.
Read more at
Penn Engineering
.
Share this article
Threads
Credits
Writer
Ian Scheffler
More from
School of Engineering & Applied Science
Genetics
Bioengineering
Research
Faculty
Graduate Students
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Health & Medicine
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Research led by Penn Dental’s Henry Daniell investigates the use of a lettuce-based, plant-encapsulated delivery platform as a new oral delivery of two GLP-1 drugs previously approved by the FDA in injectable form.
No brain, no gain: Neuronal activity enhances benefits of exercise
Image: Sciepro/Science Photo Library via Getty Images
Natural Sciences
No brain, no gain: Neuronal activity enhances benefits of exercise
Research led by Penn neuroscientist J. Nicholas Betley and collaborators finds that hypothalamic neurons are essential for translating physical exertion into endurance, potentially opening the door to exercise-mimicking therapies.
Studying Shakespeare through the lens of love
In honor of Valentine's Day, and as a way of fostering community in her Shakespeare in Love course, Becky Friedman took her students to the University Club for lunch one class period. They talked about the movie "Shakespeare in Love," as part of a broader conversation on how Shakespeare's works are adapted.
nocred
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In Becky Friedman’s English course Shakespeare in Love, undergraduate students analyze language, genre, and adaptation in the Bard’s plays through the lens of love.
Beating the heat: Designing cooling for bodies in motion
nocred
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Dorit Aviv, director of Weitzman’s Thermal Architecture Lab, studies how humans, technology, and design intersect, paving the way for the development of novel approaches to cooling people efficiently.