Human Endogenous Retrovirus with Foamy-Like Properties and Uses Thereof

Abstract

The invention relates to the discovery of a human endogenous retrovirus (HERV) family, Type I HERV-K (HML-2) which appear to be active in vitro and in vivo, infectious, and which have the have the salient features and properties of foamy retroviruses. Based on its natural replication in humans, and that it protects the host from viral and tumor transformation, this non-pathogenic endogenous virus could be developed as a replication competent gene therapy vector. It also is expected to have much higher efficacy than other vectors as it crosses the bloodbrain barrier and infects almost all cell types in the host (proliferating or not). It may naturally lyse tumor cells or infected cells, and thus could even be used without genetic modification. Of course, this vector could be used in traditional ways with it ability to replicate genetically removed. In addition to its value as a vector, as it is reactivated with infection, its detection could also be used to monitor the safety of gene therapy (irrespective of vector type used), as well as other biological therapies including vaccination, blood transfusion, transplantation and xenotransplantation. Finally it may be used to screen for new therapeutic and prophylactic treatments for a wide variety of diseases.

1 . A vector system comprising a nucleic acid molecule encoding a functional HERV Type I pol polypeptide. 
     
     
         2 . The vector system according to  claim 1  wherein the polypeptide has at least 80% homology to SEQ ID NO. 2. 
     
     
         3 . The vector system according to  claim 1  including a nucleic acid molecule encoding a therapeutic insert. 
     
     
         4 . A method of recovering HERV particles comprising:
 (a) providing a quantity of cells comprising a functional HERV Type I;   (b) incubating the cells under conditions inducing HERV Type I expression; and   (c) recovering HERV-like particles.   
     
     
         5 . The method according to  claim 4  including transforming said cells with a vector system comprising a nucleic acid molecule encoding a polypeptide having at least 80% homology to SEQ ID NO. 2 prior to step (a). 
     
     
         6 . A method of detecting Type I HERV-element expression in a sample comprising:
 providing a sample of interest suspected of containing HERV Type I expression products;   adding an HERV Type I-specific reagent to the sample;   incubating the sample and the reagent under conditions promoting interaction between the reagent and the expression products if present; and   detecting interaction between the reagent and the expression products, wherein a positive signal indicates that the expression products are present in the sample and a negative signal indicates that the expression products are not present in the sample.   
     
     
         7 . A method of identifying an agent capable of modulating HERV Type I activation comprising:
 adding a test agent to a sample comprising at least one HERV Type I element; and determining if the test agent 1) activates HERV Type I as indicated by expression of HERV Type I wherein said expression is greater than HERV Type I expression in a HERV Type I expression control or 2) inhibits HERV Type I as indicated by a lower HERV Type I expression compared to a control.