Anellovirus compositions and methods of use

Abstract

This invention relates generally to viral vectors and viral particles based on Anelloviruses, which can be used to deliver an agent (e.g., an exogenous effector or an endogenous effector, e.g., a therapeutic effector) to a cell (e.g., a cell in a subject to be treated therapeutically). Described herein are anellosomes, anellovectors, and compositions and uses thereof.

What is claimed is: 
     
         1 . An isolated cell comprising a particle comprising:
 (i) a proteinaceous exterior comprising an Anellovirus ORF1 polypeptide, and   (ii) a genetic element encapsulated by the proteinaceous exterior;   wherein the genetic element is capable of binding to the Anellovirus ORF1 polypeptide; and   wherein the genetic element comprises:   (a) a promoter operably linked to a heterologous sequence encoding a therapeutic polypeptide or nucleic acid; and   (b) an Anellovirus 5′ UTR.   
     
     
         2 . The isolated cell of  claim 1 , further comprising a nucleic acid molecule encoding the Anellovirus ORF1 polypeptide. 
     
     
         3 . The isolated cell of  claim 1 , wherein the genetic element does not comprise any sequence encoding Anellovirus ORF 1. 
     
     
         4 . The isolated cell of  claim 1 , wherein the genetic element does not comprise any sequence encoding Anellovirus ORF2. 
     
     
         5 . The isolated cell of  claim 1 , wherein the genetic element does not comprise any sequence encoding Anellovirus ORF3. 
     
     
         6 . The isolated cell of  claim 1 , wherein the genetic element:
 does not comprise any sequence encoding Anellovirus ORF1;   does not comprise any sequence encoding Anellovirus ORF2; and   does not comprise any sequence encoding Anellovirus ORF3.   
     
     
         7 . The isolated cell of  claim 1 , wherein the genetic element:
 does not comprise any sequence encoding Anellovirus ORF1 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF1;   does not comprise any sequence encoding Anellovirus ORF2 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF2; and   does not comprise any sequence encoding Anellovirus ORF3 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF3.   
     
     
         8 . The isolated cell of  claim 1 , wherein the isolated cell is a human cell. 
     
     
         9 . The isolated cell of  claim 1 , further comprising a nucleic acid encoding ORF2. 
     
     
         10 . The isolated cell of  claim 9 , wherein the nucleic acid encoding ORF2 is the same as a nucleic acid molecule encoding the Anellovirus ORF1 polypeptide of (i). 
     
     
         11 . The isolated cell of  claim 9 , wherein the nucleic acid encoding ORF2 is different from a nucleic acid molecule encoding the Anellovirus ORF1 polypeptide of (i). 
     
     
         12 . A population of the isolated cells of  claim 1 . 
     
     
         13 . An isolated cell comprising:
 (i) a nucleic acid molecule encoding an Anellovirus ORF1 polypeptide, and   (ii) a genetic element capable of binding to the Anellovirus ORF1 polypeptide;   wherein the genetic element comprises:   (a) a promoter operably linked to a heterologous sequence encoding a therapeutic polypeptide or nucleic acid; and   (b) an Anellovirus 5′ UTR.   
     
     
         14 . The isolated cell of  claim 13 , wherein the nucleic acid encoding the Anellovirus ORF1 polypeptide is a plasmid, is a viral nucleic acid, or is integrated into a cell chromosome. 
     
     
         15 . The isolated cell of  claim 13 , wherein the genetic element:
 does not comprise any sequence encoding Anellovirus ORF1;   does not comprise any sequence encoding Anellovirus ORF2; and/or   does not comprise any sequence encoding Anellovirus ORF3.   
     
     
         16 . The isolated cell of  claim 13 , wherein the genetic element:
 does not comprise any sequence encoding Anellovirus ORF1 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF1;   does not comprise any sequence encoding Anellovirus ORF2 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF2; and/or   does not comprise any sequence encoding Anellovirus ORF3 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF3.   
     
     
         17 . An isolated cell comprising:
 (i) a plurality of Anellovirus ORF1 polypeptides, and   (ii) a genetic element capable of binding to at least one of the Anellovirus ORF1 polypeptides;   wherein the genetic element comprises:   (a) a promoter operably linked to a heterologous sequence encoding a therapeutic polypeptide or nucleic acid; and   (b) an Anellovirus 5′ UTR.   
     
     
         18 . The isolated cell of  claim 17 , further comprising a nucleic acid molecule encoding the Anellovirus ORF1 polypeptide. 
     
     
         19 . The isolated cell of  claim 17 , wherein the genetic element:
 does not comprise any sequence encoding Anellovirus ORF1;   does not comprise any sequence encoding Anellovirus ORF2; and/or   does not comprise any sequence encoding Anellovirus ORF3.   
     
     
         20 . The isolated cell of  claim 17 , wherein the genetic element:
 does not comprise any sequence encoding Anellovirus ORF1 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF1;   does not comprise any sequence encoding Anellovirus ORF2 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF2; and/or   does not comprise any sequence encoding Anellovirus ORF3 or comprises a nucleic acid sequence encoding nonfunctional Anellovirus ORF3.