Compositions and Methods for Delivering Molecular Cargo to Cells

Patent Status

Patent Pending

Brief Description

Efficient delivery and expression of exogenous proteins in cell populations (e.g., cells in the body) for gene therapy / gene editing applications, is an important goal in biomedicine. This can be hampered by inefficient transport of enzymes from outside the body to cells within the body. When delivering nucleic acids or proteins of interest (e.g., DNA editing enzymes), most delivery methods can only reach and enter a small subset of cells within a tissue. There is a need for compositions and methods for improved delivery of proteins of interest, and such is provided herein.

UC Berkeley researchers have discovered that delivery of a molecular cargo to a target cell can be more efficiently achieved by using a cell as the delivery vehicle. This can be accomplished by delivering a nucleic acid encoding an enveloped delivery vehicle (EDV) (one that comprises a molecular cargo), to a producer cell where the producer cell produces the EDV and thereby delivers the molecular cargo to neighboring cells (referred to herein as receiver cells). Thus, there is no human intervention between delivery of a subject nucleic acid (encoding the EDV) and subsequent delivery of EDVs to target cells (receiver cells). 

Suggested uses

• Direct in vivo delivery of CRISPR-Cas genome editing machinery to treat genetic disorders such as Duchenne muscular dystrophy
• Targeted gene therapy for tissues with typically low transfection efficiency, such as the liver or muscle
• Local secretion and distribution of therapeutic proteins or antibodies directly at a disease site.
• Research tools for studying cell-to-cell molecular transport and localized cargo propagation

Advantages

• Utilizes host cells to produce and spread delivery vehicles, extending the therapeutic reach beyond the primary injection site
• Removes the need for complex and costly ex vivo production and purification of delivery particles
• Achieves broad tissue-level editing even with low initial transfection rates
• Integrates easily with existing delivery platforms, including lipid nanoparticles and viral vectors
• Employs a minimal structural protein that streamlines assembly and can be programmed for specific cell tropism