Improving the Efficiency of Gene Delivery to the Brain

Researchers from Rice University conducted tests to assess the safety and feasibility of gene delivery to various brain regions using a noninvasive technique based on ultrasound in rodents. Their findings indicate that the effectiveness of gene delivery increases within each specific targeted site as more sites are opened.

The lead author of the study, published in the journal Gene Therapy, is Shirin Nouraein, a Doctoral Student who works in the laboratory of Rice bioengineer Jerzy Szablowski.

The study sheds light on the research conducted by the Szablowski lab, which involves utilizing focused ultrasound energy to safely render the blood-brain barrier permeable. This technique is referred to as focused ultrasound blood-brain barrier opening (FUS-BBBO).

Additionally, this procedure allows for the movement of proteins and other small molecules in the opposite direction, specifically from the brain into the bloodstream. This facilitates easy sampling of these substances.

We use focused ultrasound to open nano-sized pores in the brain’s endothelium. This permits the noninvasive delivery of naturally occurring viral vectors throughout the brain, which is important in the treatment of genetic disorders.”

Shirin Nouraein, Graduate Student, Systems, Synthetic and Physical Biology, Rice University

As mentioned by Szablowski, who serves as an Assistant Professor of Bioengineering and Director of the Laboratory for Noninvasive Neuroengineering, numerous disorders impact substantial brain regions or even the entire brain. However, delivering gene therapy to these extensive regions poses significant challenges.

When a gene-delivery vector is injected into the brain with a needle, it often only diffuses a few millimeters. 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.”

Jerzy Szablowski, Assistant Professor, Bioengineering, Rice University

Nouraein and her research colleagues conducted experiments to assess the efficiency and safety of simultaneously opening 105 sites, yielding positive outcomes in most brain regions. Remarkably, their findings indicate that the effectiveness of gene delivery within each specific targeted site actually improves when more sites are simultaneously 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. Shirin just started her second year in graduate school and has already led an important, complex project, showing exceptional productivity and talent.”

Jerzy Szablowski, Assistant Professor, Bioengineering, Rice University