Compositions and methods for delivery of agents for neuronal regeneration and survival

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a tissue specific promoter.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter selected from the group consisting of GAP43 promoter, GFAP promoter, neuron specific enolase promoter, FGF-receptor promoter, elastase I gene control region, immunoglobulin gene control region, alpha-1-antitrypsin gene control region, beta-globin gene control region, myelin basic protein gene control region, myosin light chain 2 gene control region, RSV promoter, vaccinia virus 7.5K promoter, SV40 promoter, HSV promoter, MLP adenovirus promoter, MMTV LTR promoter, CMV promoter, metallothionein promoter, a promoter having at least one cAMP response element, tie promoter, VCAM-1 promoter, alpha V-beta 3 integrin promoters, ICAM-3 promoter, CD44 promoter, CD40 promoter, notch 4 promoter, and an event type-specific promoter.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a neuronal cell specific promoter.

A device for promoting neuronal regeneration or survival, comprising a gene activated matrix comprising a biocompatible matrix and a complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;

• wherein the vector construct comprises a promoter;
• and wherein the neurotrophic factor is selected from the group consisting of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), cardiotrophin-1 (CT-1), choline acetyltransferase development factor (CDF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM);
• glial cell-line-derived neurotrophic factor (GDNF), insulin, insulin-like growth factor-1 (IGF-1), IGF-2, interleukin-6 (IL-6), leukemia inhibitor factor (LIF), neurite promoting factor (NPF), neurotrophin-3 (NT-3), NT-4, platelet-derived growth factor (PDGF), protease nexin-1 (PN-1), S-100, transforming growth factor-β (TGF-β) and vasoactive intestinal peptide (VIP).

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is non-covalently associated with the gene activated matrix.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is adsorbed to the gene activated matrix.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is absorbed to the gene activated matrix.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is capable of inducing neuronal axonal generation or regeneration.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the neurotrophic factor is capable of maintaining axonal generation or regeneration.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is an implant for a neuronal injury site.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is formed upon administration.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is a composition selected from the group consisting of a solution, a paste, a suspension, a powder, a semisolid, an emulsion and a gel.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is a paste.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the receptor targeting ligand is capable of binding a neuronal cell surface receptor.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the receptor targeting ligand is conjugated to the vector construct and is capable of binding a neuronal cell surface receptor.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and said nucleic acid binding domain binds to a nucleic acid sequence that forms a portion of the vector construct.

A device for promoting neuronal regeneration, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and a conduit having a lumen.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises an inducible promoter.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a tissue specific promoter.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter selected from the group consisting of GAP43 promoter, GFAP promoter, neuron specific enolase promoter, FGF-receptor promoter, elastase I gene control region, immunoglobulin gene control region, alpha-1-antitrypsin gene control region, beta-globin gene control region, myelin basic protein gene control region, myosin light chain 2 gene control region, RSV promoter, vaccinia virus 7.5K promoter, SV40 promoter, HSV promoter, MLP adenovirus promoter, MMTV LTR promoter, CMV promoter, metallothionein promoter, a promoter having at least one cAMP response element, tie promoter, VCAM-1 promoter, alpha V-beta 3 integrin promoters, ICAM-3 promoter, CD44 promoter, CD40 promoter, notch 4 promoter, and an event type-specific promoter.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a neuronal cell specific promoter.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is non-covalently associated with the gene activated matrix.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is adsorbed to the gene activated matrix.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is absorbed in the gene activated matrix.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter and is capable of inducing neuronal axonai generution or regeneration.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the neurotrophic factor is capable of maintaining axonal generation or regeneration.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is an implant for a neuronal injury site.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is formed upon administration.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is a composition selected from the group consisting of a solution, a paste, a suspension, a powder, a semisolid, an emulsion and a gel.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the gene activated matrix is a paste.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the receptor targeting ligand is capable of binding a neuronal cell surface receptor.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and the receptor targeting ligand is conjugated to the vector construct and is capable of binding a neuronal cell surface receptor.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and said nucleic acid binding domain binds to a nucleic acid sequence that forms a portion of the vector construct.

A device for promoting neuronal survival, comprising:

• a gene activated matrix comprising a biocompatible matrix and complex comprising a receptor targeting ligand, a nucleic acid binding domain and a non-viral vector construct encoding a neurotrophic factor;
• wherein the vector construct comprises a promoter, and a conduit having a lumen.