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Home Gene Therapy Hydrogel-compositions-for-controlled-delivery-of-virus-vectors-and-methods-of-use-thereof

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 Hydrogel compositions for controlled delivery of virus vectors and methods of use thereof

Details
Inventors: Levy, Robert J.; Crombleholme, Timothy; Vyavahare, Narendra;
Assignee: The Children's Hospital of Philadelphia (Philadelphia, PA)
Primary Examiner: Wang; Andrew
Assistant Examiner: Zara; Jane
Attorney, Agent or Firm: Foley & Lardner

The invention relates to compositions and methods for delivering a virus vector to an animal. The compositions include compositions which comprise a hydrogel matrix (e.g. a collagen matrix which can comprise a poloxamer or an alginate) containing a virus vector therein in a transfectious form. The invention also includes methods of making such hydrogel precursor mixtures and hydrogel matrices, including particles, devices, bulk materials, and other objects which comprise, consist of, or are coated with such mixtures or matrices. The invention further relates to compositions comprising a hydrogel precursor mixture having a virus vector suspended therein, which, when administered to an animal, gel to form a hydrogel matrix containing a virus vector therein in a transfectious form. Methods of delivering a virus vector to an animal tissue are also described.

DETAILED DESCRIPTION The invention relates to a composition for delivery of a virus vector to an animal cell.
The composition comprises a hydrogel precursor mixture having the virus vector suspended therein.
The hydrogel precursor mixture is formulated such that it stiffens at physiological temperature and at a physiological calcium level to form a hydrogel matrix containing the virus vector therein in a transfectious form.
In one embodiment of the composition described herein, the hydrogel matrix is biodegradable, such as with a collagen hydrogel precursor mixture.
When collagen is used, it is preferably type I collagen, such as bovine type I collagen.
The biodegradable hydrogel matrix can be made using a precursor mixture which further comprises another component selected from the group consisting of a poloxamer and an alginate.
Furthermore, the virus vector can be linked with another component of the hydrogel precursor mixture, such that when the hydrogel matrix is formed, the virus vector is linked with the hydrogel matrix.
Substantially any virus vector can be used in the hydrogel matrix described herein, such as one selected from the group consisting of an adenovirus vector, a lentivirus vector, a retrovirus vector, an adeno-associated virus vector, and a herpesvirus vector.
Preferably, the virus vector is an adenovirus vector.
In one embodiment, the hydrogel precursor mixture further comprises an additional component selected from the group consisting of a polycation, a second virus vector, the protein of a protein-ligand pair, and the ligand of a protein-ligand pair.
The polycation can, for example, be selected from the group consisting of polylysine, polyarginine, polyornithine, polyhistidine, myelin basic protein, a low molecular weight glycopeptide, a cationic amphiphilic alpha-helical oligopeptide having a repeating sequence, a histone, a galactosylated histone, polybrene, spermine, spermidine, prolamine, polyethylenimine, putrescine, cadaverine, and hexamine.
Preferably, the polycation is poly-L-lysine



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