Fiber shaft modifications for efficient targeting
AssigneesNovartis AG, The Scripps Research Institute
InventorsMichael Kaleko, Glen R. Nemerow, Theodore Smith, Susan C. Stevenson
Life of this patent
Estimating the term…
Abstract
Provided are adenoviral vectors and the production of such vectors. In particular, fiber shaft modifications for efficient targeting of adenoviral vectors are provided. The fiber shaft modifications can be combined with other modifications, such as fiber knob and/or penton modifications, to produce fully ablated (detargeted) adenoviral vectors. A scale-up method for the propagation of detargeted adenoviral vectors is also provided.
Claims70
A modified adenovirus capsid protein,
- the unmodified capsid protein binds to heparin sulfate proteoglycan (HSP);
- and
- the capsid protein comprises a mutation, whereby binding to heparin sulfate proteoglycan (HSP) is altered.
The adenoviral vector of claim 56, wherein the heterologous nucleic acid comprises or encodes a promoter or RNA.
A method of reducing transduction of liver cells by an adenoviral particle, comprising reducing or eliminating binding of the particle to heparin sulfate proteoglycans (HSPs) on the liver cells.
A scale up method for the propagation of a detargeted adenoviral particle, comprising:
- infecting a cell capable of replicating, maturing and packaging an adenoviral vector with a detargeted adenoviral vector in the presence of a reagent that results in entry of the adenoviral particle into the cell;
- culturing the infected cell under conditions suitable for growth, spread and propagation of the adenoviral vector;
- and
- recovering the resulting adenoviral particles.
Dependencies are inferred from the claim text.