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Ultrasound enables gene delivery throughout the brain

Rice study uncovers way to efficiently deliver clinically used gene therapy vectors

Ultrasound enables gene delivery throughout the brain
2023-09-27
(Press-News.org) HOUSTON – (Sept. 27, 2023) – Rice University researchers tested the safety and feasibility of gene delivery to multiple brain regions using a noninvasive, ultrasound-based technique in rodents, and their findings suggest that the efficiency of gene delivery improves within each targeted site when more sites are opened.

Shirin Nouraein, a doctoral student working in the lab of Rice bioengineer Jerzy Szablowski, is the lead author on the study recently published in the journal Gene Therapy.

The paper, “Acoustically Targeted Noninvasive Gene Therapy in Large Brain Volumes,” continues the Szablowski lab’s work using focused ultrasound energy to safely make the blood-brain barrier permeable. The technique is known as focused ultrasound blood-brain barrier opening (FUS-BBBO).

The procedure also permits the passage of proteins and other small molecules in the other direction ⎯ that is, from the brain into the bloodstream ⎯ where they can be readily sampled.

“We use focused ultrasound to open nano-sized pores in the brain’s endothelium,” said Nouraein, a graduate student in systems, synthetic and physical biology. “This permits the noninvasive delivery of naturally occurring viral vectors throughout the brain, which is important in the treatment of genetic disorders.”

Many disorders affect large brain regions or the entire brain, but delivery of gene therapy to these regions is difficult, said Szablowski, assistant professor of bioengineering and director of the Laboratory for Noninvasive Neuroengineering.

“When a gene-delivery vector is injected into the brain with a needle, it often only diffuses a few millimeters,” Szablowski said. “To treat the entire brain, one would need to perform thousands of injections, which would be difficult and possibly harmful. With FUS-BBBO, such surgical delivery could be circumvented.”

Nouraein and her research collaborators tested the efficiency and safety of opening 105 sites simultaneously with positive results in most regions of the brain. Surprisingly, their findings suggest that the efficiency of gene delivery improves within each targeted site when more sites are opened.

“We found that delivery of the vectors throughout the brain doubles the efficiency of delivery for the same dose of the virus compared to when only 11 sites are targeted,” Szablowski said, adding that Nouraein played a major role in making the discovery

“Shirin just started her second year in graduate school and has already led an important, complex project, showing exceptional productivity and talent,” Szablowski said.

The research was supported by the John S. Dunn Foundation and the Welch Foundation (C-2048-20200401).

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For more Rice News go to news.rice.edu.

Follow Rice News and Media Relations via Twitter @RiceUNews .

This release was authored by Patrick Kurp, science writer for the George R. Brown School of Engineering.

Peer-reviewed publication:

“Acoustically targeted noninvasive gene therapy in large brain volumes” | Gene Therapy | DOI: 10.1038/s41434-023-00421-1

Authors: Shirin Nouraein, Sangsin Lee, Vidal Saenz, Huckie Del Mundo, Joycelyn Yiu and Jerzy Szablowski

https://doi.org/10.1038/s41434-023-00421-1

Image downloads:

https://news-network.rice.edu/news/files/2023/09/Shirin-Nouraein.jpg
CAPTION: Shirin Nouraein is a Rice University Ph.D. student and lead author on a paper recently published in Gene Therapy.
(Photo courtesy of the Laboratory for Noninvasive Neuroengineering/Rice University)

Related stories:

DARPA grant will fund hunt for drug that can keep people warm:
https://news.rice.edu/news/2023/darpa-grant-will-fund-hunt-drug-can-keep-people-warm

Rice bioengineer seeks better signals from cells:
https://news.rice.edu/news/2022/rice-bioengineer-seeks-better-signals-cells

Three research teams earn Dunn Awards:
https://news.rice.edu/news/2020/three-research-teams-earn-dunn-awards

Links:

Laboratory for Noninvasive Neuroengineering (Szablowski lab): https://www.szablowskilab.org/

Rice Neuroengineering Initiative: https://neuroengineering.rice.edu/

Department of Bioengineering: https://bioengineering.rice.edu

George R. Brown School of Engineering: https://engineering.rice.edu

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. 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 4,552 undergraduates and 3,998 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 4 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.

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[Press-News.org] Ultrasound enables gene delivery throughout the brain
Rice study uncovers way to efficiently deliver clinically used gene therapy vectors