Rice bioengineers look for better signals from cells

The cells in your body are very good at self-monitoring, but they don't always send signals
to the outside world.
A bioengineer at Rice University plans to improve their communication skills
.

Jerzy Szablowski, an assistant professor of bioengineering at Rice University, is developing techniques
to measure gene expression in deep tissues, particularly the brain.
His non-invasive, site-specific reporters will be secreted by cells to report their findings
.

This is particularly useful for monitoring gene therapies for neurodegenerative diseases such as epilepsy, amyotrophic lateral sclerosis, or Huntington's disease, because modified cells can make their own drugs and also make proteins
that confirm their expression.

Szablowski's research is now supported by the National Institutes of Health to develop these reporters through a three-year exploratory/developmental research grant, aka the Trailblazer Award, that can be easily transported from known regions of the brain into the bloodstream
.
A simple blood test can then be used to analyze them
.

"This is a critical question in gene therapy research," said
Szablowski, assistant professor of bioengineering.
"In most cases, once treatment is administered, there is little way to assess whether a gene is expressed
in cells deep in the body.

"There are markers that tell you naturally about the disease, but there are also diseases or processes that are not marked in the blood, which is inconvenient
," he said.
"So why not flag these processes so they're easy to spot?" Why not give cells the ability to inform us about these diseases?"

The solution proposed by Szablowski is simple and elegant
.
Reporter molecules are marker molecules of cells that are only generated
when they contain newly transmitted genes.
The number of reporter genes in a sample is often a measure of the success of gene delivery therapy: the greater the number of reporters, the more
cells receive and absorb new genes.

Finding and measuring tissue samples
, usually through microscopic analysis, is sought and measured.
In clinical trials, such samples can only come from major surgery, which is often either not financially feasible, too risky for the patient, or both
.

"It's impractical or impossible to take tissue under the microscope, but if we can engineer reporter cells so that they leave the cell and enter the bloodstream, we don't have to
," Szablowski said.

If this approach works as expected, measuring the success of gene therapy in any tissue in the body could be as simple
as drawing blood and submitting it for lab tests.

To demonstrate the technology, Szablowski is designing a reporter that can tell if gene expression is happening in the brain, one of the most inaccessible parts of
the body.
This means having cell-expressed journalists cross the blood-brain barrier into the bloodstream, where they can be collected
.

His lab's strategy is to increase vascular permeability in specific areas of the brain, allowing proteins to spread into the bloodstream
.
The project will also include protein engineering, pharmacology and biodistribution studies, as well as gene delivery to the brain
.

Szabrowski said the same technique could be applied to the spinal cord, eyes, ears and possibly other tissues
.