DELIVERY OF CRISPR COMPONENTS

Researchers at UC Berkeley have developed novel strategies for the delivery of CRISPR gene editing components.

While CRISPR-based gene editing holds great promise for treating genetic diseases, it often involves DNA breaks or base changes that can cause off-target effects, cell damage, or unpredictable outcomes. Additionally, these changes are often permanent and may lead to harmful consequences. Epigenetic editing offers a safer alternative by enabling reversible, long-term regulation of gene expression without altering the DNA sequence itself. This approach also allows for more versatile editing of both DNA and histone epigenetic markers, though achieving efficient and durable delivery remains a key challenge.

Stage of Research

This invention introduces a cutting-edge virus-like particle (VLP) platform designed to deliver precise, reversible epigenetic editing tools directly into cells—offering a safer alternative to traditional gene editing. These VLPs carry a customizable therapeutic cargo that combines a nuclease-deficient CRISPR protein with domains that chemically modify DNA or histones, enabling targeted gene silencing or activation without cutting the DNA. The system is modular and programmable, allowing it to be tailored to a wide range of genetic targets through simple changes to the guide sequence. The VLPs are produced using a scalable method involving transfection of host cells with a defined set of plasmids, ensuring efficient assembly and delivery. This technology has the potential to revolutionize gene regulation therapies by enabling highly specific, durable, and non-permanent control of gene expression across diverse disease contexts.

Applications

Targeted Gene Silencing for Disease Treatment: The VLP system can be used to epigenetically silence disease-causing genes in conditions such as cancer, neurological disorders, or autoimmune diseases—offering a precise and reversible therapeutic strategy without permanently altering the genome.
Gene Reactivation in Genetic or Epigenetic Disorders: This technology can activate or restore the expression of beneficial genes that are silenced due to epigenetic modifications, making it valuable for treating conditions like Fragile X syndrome or other imprinting disorders where gene reactivation could restore normal function.

Advantages

Safe and Reversible Gene Regulation: Unlike traditional gene editing that permanently alters DNA, this invention enables epigenetic modifications that are long-lasting yet reversible, reducing the risk of off-target effects and irreversible genetic damage.
Efficient, Non-Integrating Delivery System: The use of virus-like particles (VLPs) allows for efficient delivery of therapeutic cargo into target cells without integrating into the host genome, enhancing safety while maintaining high gene modulation efficacy across multiple cell types.