Fiber shaft modifications for efficient targeting
AssigneesThe Scripps Research Institute, Novartis AG
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.
Claims26
An adenoviral particle, comprising a heterologous fiber, whereby binding of the viral particle to heparin sulfate proteoglycans (HSP) is reduced or eliminated compared to a particle that expresses its native fiber, wherein:
- the adenoviral (Ad) particle, except for the fiber, is from a subgroup C adenovirus;
- and
- the fiber is from an adenovirus selected from the group consisting of Ad3, Ad35, Ad7, Ad11, Ad16, Ad21, Ad34, Ad40 short fiber, Ad41 short fiber, Ad8, Ad9, Ad10, Ad13, Ad15, Ad17, Ad19, Ad20, Ad22, Ad23, Ad24, Ad25, Ad26, Ad27, Ad28, Ad29 Ad30, Ad32, Ad33, Ad36, Ad38, Ad39, Ad42, Ad43, Ad44, Ad45, Ad46, Ad47, Ad48 and Ad49.
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, wherein:
- the adenoviral (Ad) particle comprises heterologous fiber;
- the particle is derived from a subgroup C adenovirus;
- and
- the fiber is from an adenovirus from a subgroup B, D or F adenovirus.
A nucleic acid molecule, comprising a modified genome of a group C adenovirus, wherein the modification comprises replacement of native fiber encoding nucleotides with those encoding a heterologous fiber from an adenovirus selected from the group consisting of Ad3, Ad35, Ad7, Ad11, Ad16, Ad21, Ad34, Ad40 short fiber, Ad41 short fiber, Ad8, Ad9, Ad10, Ad13, Ad15, Ad17, Ad19, Ad20, Ad22, Ad23, Ad24, Ad25, Ad26, Ad27, Ad28, Ad29 Ad30, Ad32, Ad33, Ad36, Ad38, Ad39, Ad42, Ad43, Ad44, Ad45, Ad46, Ad47, Ad48 and Ad49, whereby an adenoviral particle that comprises the nucleic acid molecule expresses the heterologous fiber.
Dependencies are inferred from the claim text.