Targeted gene transfer into developmentally defined cell populations of the primate brain

Area of Science:

• Neuroscience
• Genetics
• Primate Research

Background:

• Investigating primate brain development and function is limited by a lack of effective genetic tools.
• Existing methods for gene transfer in primates are insufficient for systematic study.

Purpose of the Study:

• To develop a minimally invasive and versatile method for gene transfer in the fetal primate brain.
• To enable widespread and targeted transgene expression for neuroscience research.

Main Methods:

• Ultrasound-guided fetal intracerebroventricular viral injections (FIVI) using recombinant adeno-associated viruses (rAAVs).
• Optimization of gestational timing, viral serotypes, and regulatory elements for targeted gene delivery.
• Demonstration of laminar expression, Cre-dependent targeting, CRISPR gene editing, and pathway labeling.

Main Results:

• Achieved rapid-onset, long-lasting transgene expression across the primate cerebral cortex.
• Successfully targeted specific cell populations and neuronal types.
• Demonstrated the ability to perform gene editing and label neural pathways.

Conclusions:

• Fetal intracerebroventricular viral injections (FIVI) provide an efficient and targeted method for gene transfer in the fetal primate brain.
• This technique overcomes limitations of current models, opening new avenues for experimental and translational neuroscience.
• The method mimics desirable features of germline transgenic models for comprehensive lifespan studies.