image: Rice bioengineer Jerzy Szablowski won an NIH Trailblazer Award for developing noninvasive, site-specific cell-secreted reporters to measure gene expression in deep tissues, particularly in the brain.
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Credit: Jeff Fitlow/Rice University
HOUSTON – (November 10, 2022) – Your body’s cells are pretty good at monitoring themselves, but they don’t always signal what’s going on to the outside world. A Rice University bioengineer plans to improve his ability to communicate.
Jerzy Szablowski, assistant professor of bioengineering at Rice’s George R. Brown School of Engineering, is developing technology to measure gene expression in deep tissues, particularly in the brain. Its non-invasive, site-specific reporters will be secreted by cells to report what they find.
This could be particularly useful for monitoring gene therapy treating neurodegenerative disorders like epilepsy, amyotrophic lateral sclerosis or Huntington’s disease, as cells engineered to make their own drugs would also make proteins that would confirm their expression.
Szablowski’s research is now supported by the National Institutes of Health through a three-year Exploratory/Developmental Research Grant (aka Trailblazer Award) to develop these reporters, which can be easily transported from known regions of the brain into the blood. Then a simple blood test can be used to analyze them.
“This is a critical issue in gene therapy research,” said Szablowski, an assistant professor of bioengineering. “In most cases, once therapy is given, there are few or no methods to assess whether genes are being expressed in cells deep within the body.
“There are markers that naturally tell you about disease, but there are also diseases or processes that don’t have markers in the blood, and that’s embarrassing,” he said. “So why not create markers for these processes so that they are easy to detect? Why not give cells the ability to inform us about these diseases?
The solution proposed by Szablowski is elegant in its simplicity. Reporters are the marker molecules that cells are programmed to make only if they have incorporated the newly delivered genes. The amount of reporters in a sample is often an indicator of the success of gene delivery therapy: the more reporters, the more cells that have accepted and incorporated the new genes.
The search for and measurement of reporters is usually done by microscopic analysis of tissue samples. In clinical trials, such samples could only come from major surgery, which is often either financially unfeasible, too risky for patients, or both.
“It’s impractical or impossible to get the tissue under the microscope, but we don’t have to if we can engineer the reporters to leave the cells and enter the bloodstream,” Szablowski said. .
If the method works as expected, measuring the success of gene therapy in any tissue in the body could be as simple as drawing blood and subjecting it to laboratory tests.
To demonstrate the technique, Szablowski designs reporters that can tell whether gene expression is taking place in the brain, one of the most inaccessible parts of the body. This means passing cell-expressed reporters across the blood-brain barrier and into the bloodstream, where they can be collected.
His lab’s strategy is to improve vascular permeability in certain regions of the brain and allow proteins to diffuse into the blood. The project will also include studies on protein engineering, pharmacology and biodistribution, as well as gene delivery to the brain.
Szablowski said the same techniques can be applied to the spinal cord, eyes, ears and potentially other tissues.
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High resolution IMAGE available for download at:
https://news-network.rice.edu/news/files/2022/10/1031_TRAILBLAZER-1-web-SZABLWSKI.jpg
CAPTION: Jerzy Szablowski. (Photo by Jeff Fitlow/Rice University)
Associated materials:
The Packard Foundation backs Rice bioengineer: https://news.rice.edu/news/2021/packard-foundation-backs-rice-bioengineer
Noninvasive Neuroengineering Lab: https://www.szablowskilab.org
Department of Bioengineering: https://bioengineering.rice.edu
George R. Brown School of Engineering: https://engineering.rice.edu
This press release can be viewed online at https://news.rice.edu/news/2022/rice-bioengineer-seeks-better-signals-cells.
Follow Rice News and Media Relations via Twitter @RiceUNews.
Located on a 300-acre wooded campus in Houston, Rice University is consistently ranked among the top 20 universities in the nation by US News & World Report. Rice has highly respected schools of architecture, business, continuing studies, engineering, humanities, music, natural sciences, and social sciences and is home to the Baker Institute for Public Policy. With 4,240 undergraduate students and 3,972 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6 to 1. Its residential college system creates tight-knit communities and lifelong friendships, one reason for which Rice is ranked #1 for many race/class interactions and #1 for quality of life by the Princeton Review. Rice is also ranked as the best value among private universities by Kiplinger’s Personal Finance.
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