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.

Challenges in 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.

Proposed Solution

This nanoplatform will transform CRISPR into a clinically relevant, non-invasive technology, enabling therapeutic genome editing in the brain. 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.

Mechanism of Action

We will harness these unique abilities within the novel nanoplatform to:

• Shuttle CRISPR machinery across the blood-brain barrier
• Transport it into deep brain regions
• 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
• A high degree of modularity and compositional heterogeneity, thus providing both universal and patient-specific components.

Research Methodology

The nanoplatform will be thoroughly investigated in:

1. Primary brain cells
2. 3D organoids
3. Case studies of monogenic brain disease models.

Expected Outcomes

This comprehensive research will culminate in a universal and modular BrainCRISPR nanoplatform and delineate design principles for its precise tailoring to the specific needs of different brain diseases.

Conclusion

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.