Modulation of Adenoviral Tropism

A method of modulating liver or spleen infectivity of an adenovirus comprising:

• providing a parent adenoviral hexon protein;
• modifying said parent hexon protein to produce a modified hexon protein having altered affinity for FX;
• and
• producing an adenovirus comprising said modified hexon protein;
• whereby said adenovirus has altered ability to transduce hepatocytes or splenocytes compared to an adenovirus comprising said parent hexon protein, wherein the parent and modified hexon proteins differ:
• (i) in one or more of HVR3 and HVR7;
• (ii) by a point mutation in HVR5 at a residue corresponding to Thr268, Thr269 and/or Glu270 of Ad5 hexon protein [shown as Thr269, Thr270 and Glu271 in the sequence having accession nos. AAW65514.1;
• GI:
• 58177707];
• (iii) by one or more amino acids in the scaffold sequence at residues corresponding to Ser267, Met314, Asn421, Thr426, Ser446, Asn449, Glu450, Arg452 and Val453 of Ad5 hexon protein [shown as Ser268, Met315, Asn422, Thr427, Ser447, Asn450, Glu451, Arg453 and Val454 in the sequence having accession nos. AAW65514.1;
• GI:
• 58177707];
• and/or
• (iv) in that the modified hexon protein is a chimeric hexon protein in which HVR5 is derived from a hexon protein of a different serotype to the parent hexon protein.

A modified adenoviral hexon protein, which differs from a parent hexon protein

• (i) in one or more of HVR 3 and HVR7;
• (ii) by a point mutation in HVR5 at a residue corresponding to Thr268, Thr269 and/or Glu270 of Ad5 hexon protein [shown as Thr269, Thr270 and Glu271 in the sequence having accession nos. AAW65514.1;
• GI:
• 58177707];
• (iii) by one or more amino acids in the scaffold sequence at residues corresponding to Ser267, Met314, Asn421, Thr426, Ser446, Asn449, Glu450, Arg452 and Val453 of Ad5 hexon protein [shown as Ser268, Met315, Asn422, Thr427, Ser447, Asn450, Glu451, Arg453 and Val454 in the sequence having accession nos. AAW65514.1;
• GI:
• 58177707];
• and/or
• (iv) in that the modified hexon protein is a chimeric hexon protein in which HVR5 is derived from a hexon protein of a different serotype to the parent hexon protein;
• whereby an adenovirus comprising said modified hexon protein has altered ability to transduce hepatocytes or splenocytes compared to an otherwise identical adenovirus comprising said parent hexon protein.