Non-replicating virus-derived particles and uses thereof

Abstract

There is described herein a non-replicating Rhabdovirus-derived particle that lacks the ability to spread between cells while having tropism against immortalized cells. The non-replicating Rhabdovirus-derived particle may have cytolytic tropism against immortalized cells. There is also described a non-replicating Rhabdovirus-derived particle that lacks the ability to spread between cells but has innate and/or adaptive immune-stimulating properties.

What is claimed is: 
     
         1 . A product comprising a non-replicating, cell-internalizing Rhabdovirus-derived particle for treating cancer cells in a subject, wherein said Rhabdovirus-derived particle exhibits RNA which is cross-linked or cleaved into at least two discontinuous RNA polynucleotide sequences. 
     
     
         2 . The product of  claim 1 , wherein said Rhabdovirus-derived particle exhibits:
 RNA cross-linked to other RNA nucleotides, to amino acids in a protein structure around the RNA of the Rhabdovirus, or;   the protein structure around the RNA is cross-linked to another protein of the protein structure, or to another amino acid of the same protein;   or both.   
     
     
         3 . The product of  claim 1 , wherein said RNA comprises at least 0.05% cross-linked nucleotides. 
     
     
         4 . The product of  claim 1 , wherein said non-replicating, cell-internalizing Rhabdovirus-derived particle exhibits at least 60 G proteins per particle. 
     
     
         5 . The product of  claim 1  for treating cancer cells, wherein said product is for use in combination with a second pharmacological agent. 
     
     
         6 . The product of  claim 1 , produced by the method of subjecting live Rhabdovirus to an RNA damaging agent to under conditions to cross-link RNA of the Rhabdovirus, cleave the RNA structure of the Rhabdovirus or both. 
     
     
         7 . A method of treating cancer in a subject comprising, administering the product of  claim 1  to a subject in need thereof. 
     
     
         8 . The method of  claim 7  wherein about 1×10 10  to about 1×10 15  Rhabdovirus-derived particles are administered to the subject. 
     
     
         9 . The method of  claim 7 , further comprising administering a second pharmaceutical agent to the subject. 
     
     
         10 . The method of  claim 9  wherein the pharmaceutical agent is a chemotherapeutic agent. 
     
     
         11 . A method for producing the product as defined in  claim 1  comprising the step of:
 subjecting live Rhabdovirus to an RNA damaging agent under conditions to cross-link RNA of the Rhabdovirus, cleave the RNA structure of the Rhabdovirus or both to produce non-replicating, cell-internalizing Rhabdovirus-derived particles. 
 
     
     
         12 . The method of  claim 11 , wherein the RNA damaging agent is electromagnetic radiation, a chemical cross-linking agent or both. 
     
     
         13 . The method of  claim 11 , wherein the electromagnetic radiation has a wavelength less that about 1 mm. 
     
     
         14 . The method of  claim 12 , wherein the RNA damaging agent is electromagnetic radiation with a dose of between about 100 mJ/cm 2  and about 8000 mJ/cm 2  or gamma irradiation with a dose of between 1 kGy and about 50 kGy.