Virus-like Particles with Programmable Tropism and Methods of Use Thereof for Delivery to Cells

Smart overview of the Invention

The patent application details programmable tropism virus-like particles (ptVLPs) designed for targeted delivery to cells. These particles feature a phospholipid bilayer membrane with virus-derived glycoproteins, which may be modified or truncated. The glycoproteins can be directly fused to various targeting domains, such as peptides or nanobodies, to enhance specificity. Additionally, a biomolecule cargo, often linked to a membrane recruitment domain, is housed within the ptVLP core.

Technical Components

Key components of the ptVLPs include wild-type or mutant virus-derived envelope glycoproteins and targeting domains. These targeting domains can be single chain variable fragments (scFv), fibronectin type 3 domains (FN3), or other ligands. The targeting domains may bind to specific human proteins like CD19 or HER2. The ptVLPs aim to exclude human endogenous viral proteins, focusing instead on engineered viral elements.

Applications and Uses

The primary application of these ptVLPs is in the precise delivery of therapeutic agents, particularly gene editing tools like CRISPR-Cas systems. The ptVLPs can carry therapeutic proteins or nucleic acids, potentially aiding in treatments requiring targeted cellular delivery. This technology could be pivotal in both in vivo and in vitro therapeutic contexts.

Production and Methodology

Methods for producing ptVLPs involve using host cells to express the necessary fusion proteins and cargo without exogenous viral proteins. These processes might include purifying and concentrating the resultant particles. The patent also describes potential use with human cell lines like HEK 293 for production purposes.

Potential Cargo Variants

The ptVLPs can encapsulate various cargos, including gene editing reagents like zinc fingers or transcription activator-like effectors (TALEs). Cargos may also include therapeutic proteins or diagnostic molecules, expanding the potential utility of this technology in medical applications. Specific sequences for these cargos are detailed in accompanying tables within the patent.