In Vivo CRISPR-Based Nanoplatform for Gene Editing: A New Disruptive Avenue for Non-Invasive Treatment of Genetic Brain Diseases

Introduction

Genetic brain diseases are among the most devastating and fatal diseases, typically having only palliative treatments and no cure. The revolutionary CRISPR/Cas gene editing technology provides a new horizon and enormous potential for treating such diseases.

Challenge of Delivery

However, efficient and safe delivery of CRISPR machinery to diseased cells within the brain is one of the greatest challenges in medicine today. Here, I plan to expand far beyond the state-of-the-art and propose a game-changing approach for this unmet need: a breakthrough nanoplatform, which will transform CRISPR into a clinically relevant, non-invasive technology, enabling therapeutic genome editing in the brain.

Proof-of-Concept Results

Our proof-of-concept results serve as the baseline of this pioneering research project, revealing the exceptional capabilities of insulin as a key to overcoming formidable brain and cell barriers. We will harness these unique abilities within the novel nanoplatform, and:

1. Shuttle CRISPR machinery across the blood-brain barrier
2. Transport it into deep brain regions
3. Mediate its successful entry into specific diseased brain cells, leading to highly effective gene editing.

Design Criteria

The nanoplatform will be designed to meet key criteria for non-invasive, safe, and efficient delivery of CRISPR to the brain, while conferring a high degree of modularity and compositional heterogeneity. This will provide both universal and patient-specific components.

Research Methodology

The nanoplatform will be thoroughly investigated in:

• Primary brain cells
• 3D organoids
• Case studies of monogenic brain disease models

Conclusion

This comprehensive research will culminate with a universal and modular BrainCRISPR nanoplatform, and delineate design principles for its precise tailoring to the specific needs of different brain diseases. Overall, this research will provide in-depth fundamental knowledge and have a transformative effect on applying CRISPR in the brain, whilst opening a wide array of possibilities with broader impact on genetic brain therapy and beyond.