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

Smart overview of the Invention

Programmable tropism virus-like particles (ptVLPs) consist of a phospholipid bilayer membrane that is decorated with wild-type or mutant virus-derived glycoproteins on the outside. These glycoproteins can be directly fused to various targeting domains, such as peptides or nanobodies, enhancing the ability to direct the ptVLPs to specific cell types. Additionally, a biomolecule cargo can be housed within the core of the ptVLP, ideally linked to a recruitment domain that integrates with the membrane.

Targeting Domains and Fusion Proteins

The targeting domain can be linked to the virus-derived glycoproteins either at the ends or inserted into the protein structure. Options for targeting domains include a variety of ligands like single chain variable fragments (scFv) and arginylglycylaspartic acid motifs (RGD). Furthermore, fusion proteins can incorporate a membrane-anchored targeting domain, allowing for versatile configurations to enhance specificity in targeting cells.

Cargo and Therapeutic Applications

The core of ptVLPs can carry therapeutic or diagnostic agents, including proteins, nucleic acids, or small molecules. Notably, gene editing tools such as CRISPR-Cas systems can be integrated as cargo. The design ensures that the ptVLPs can deliver these agents effectively to target cells, potentially improving therapeutic outcomes in gene editing and other medical applications.

Production and Expression Methods

Methods for producing ptVLPs involve cells engineered to express specific fusion proteins along with necessary cargo. These cells are maintained under conditions favorable for VLP production without expressing viral proteins that could interfere with the process. Harvesting and purifying the produced particles are also included in the methods, enabling efficient collection for further use.

Research Funding and Rights

This innovation was developed with government support from the National Institutes of Health, which retains certain rights over the invention. The application also includes an electronic sequence listing that details specific sequences related to the described proteins and domains, further aiding in research and development efforts in this field.