Targeting of herpes simplex virus to specific receptors

摘要

The invention relates to engineered Herpes simplex virus (HSV) particles that are targeted to one or more specific binding pair members, such as receptors. Also, recombinant vectors for producing such HSV particles are provided. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention are useful for targeting cells that express the selected receptor, which itself may be a product of genetic engineering. The ability to selectively target cells render the HSV particles. particularly useful in selectively diagnosing, treating, and imaging cells bearing the selected binding pair member, such as a receptor. The invention also provides for polynucleotide-based therapy to cells bearing the selected binding pair member such as a receptor.

主权项

1. A recombinant herpes simplex virus (HSV) particle having at least one protein on its surface, comprising:
(a) an altered gD, wherein the alteration reduces binding of gD to one or more of its cellular receptors, said alteration comprising
(i) a heterologous peptide ligand on the surface of the recombinant HSV particle forming a fusion protein with the altered gD, wherein a polynucleotide encoding the fusion protein is joined to a heterologous coding region for a leader sequence; and(ii) an amino acid alteration; wherein said recombinant HSV particle preferentially binds to cells expressing a binding partner to said heterologous peptide ligand.