Cocal vesiculovirus envelope pseudotyped retroviral vectors

Abstract

Provided herein are Cocal vesiculovirus envelope pseudotyped retroviral vectors that exhibit high titers, broad species and cell-type tropism, and improved serum stability. Disclosed Cocal vesiculovirus envelope pseudotyped retroviral vectors may be suitably employed for gene therapy applications and, in particular, for the ex vivo and in vivo delivery of a gene of interest to a wide variety of target cells.

1 .- 28 . (canceled) 
     
     
         29 . A method for delivering a gene of interest to a target cell, said method comprising the step of contacting said target cell with a Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle. 
     
     
         30 . The method of  claim 29  wherein said Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle is selected from the group consisting of a lentiviral vector particle, an alpharetroviral vector particle, a betaretroviral vector particle, a gammaretroviral vector particle, a deltaretroviral vector particle, and an epsilonretroviral vector particle. 
     
     
         31 . The method of  claim 29  wherein said Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle comprises a Cocal  vesiculovirus  envelope protein encoded by the nucleotide sequence of SEQ ID NO: 1. 
     
     
         32 . The method of  claim 29  wherein said Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle comprises a Cocal  vesiculovirus  envelope protein comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         33 . The method of  claim 29  wherein said Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle comprises a Cocal  vesiculovirus  envelope protein encoded by the nucleotide sequence of SEQ ID NO: 3. 
     
     
         34 . The method of  claim 29  wherein said Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle comprises a Cocal  vesiculovirus  envelope protein comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
         35 . A method for delivering a gene of interest into a hematopoietic system of a patient, said method comprising the steps of:
 (a) harvesting a CD34 +  hematopoietic stem cell (HSC) from said patient;   (b) transducing said HSC ex vivo with a Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle comprising said gene of interest; and   (c) introducing said ex vivo transduced HSC into said patient under conditions that allow reconstitution of said patient's hematopoietic system.   
     
     
         36 . A method for identifying a patient susceptible to treatment with a Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle; said method comprising the steps of:
 (a) isolating a serum sample from said patient;   (b) contacting said Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle with said serum sample; and   (c) testing said Cocal  vesiculovirus  envelope pseudotyped retroviral vector particle for serum inactivation.