# US 7,892,809 B2 · Chimeric vectors

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- Number: US 7,892,809 B2
- Document ID: US7892809B2
- Status: Granted
- Kind: B2
- Application number: 11/793,430
- Filed: 2005-12-15
- Published: 2008-10-30
- Granted: 2011-02-22
- Earliest claimed: 2004-12-15
- Assignees: The University of North Carolina at Chapel Hill; University of Florida Research Foundation, Inc.
- Inventors: Dawn E. Bowles; Chengwen Li; Joseph E. Rabinowitz; Josh Grieger; Mavis Agbandje-McKenna; Richard Jude Samulski
- Web page: https://patentgrep.com/patent/US7892809B2

## CPC

- C12N 15/86: Viral vectors
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 13/12: of the kidneys
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 2750/14122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C12N 2750/14144: Chimeric viral vector comprising heterologous viral elements for production of another viral vector
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is based, in part, on the discovery that parvovirus (including AAV) capsids can be engineered to incorporate small, selective regions from other parvoviruses that confer desirable properties. The inventors have discovered that in some cases as little as a single amino acid insertion or substitution from a first parvovirus (e.g., an AAV) into the capsid structure of another parvovirus (e.g., an AAV) to create a chimeric parvovirus is sufficient to confer one or more of the desirable properties of the first parvovirus to the resulting chimeric parvovirus and/or to confer a property that is not exhibited by the first parvovirus or is present to a lesser extent.

## Claims

### Claim 1

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid insertion immediately following amino acid position 264 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AAV a capsid subunit from other AAV; and
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 2 (depends on 1)

The chimeric virus vector of claim 1, wherein said chimeric virus vector has enhanced transduction of a target cell as compared with the recipient parent AAV vector.

### Claim 3 (depends on 2)

The chimeric virus vector of claim 2, wherein said chimeric virus vector has enhanced transduction of skeletal muscle.

### Claim 4 (depends on 2)

The chimeric virus vector of claim 2, wherein said chimeric virus vector has enhanced transduction of cardiac muscle.

### Claim 5 (depends on 2)

The chimeric virus vector of claim 2, wherein said chimeric virus vector has enhanced transduction of astrocytes and/or glial cells.

### Claim 6 (depends on 1)

The chimeric virus vector of claim 1, wherein the insertion is an insertion of threonine into the capsid subunit.

### Claim 7 (depends on 1)

The chimeric virus vector of claim 1, wherein the chimeric virus vector comprises a chimeric AAV2 capsid comprising an amino acid insertion immediately following amino acid position 264 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3).

### Claim 8 (depends on 7)

The chimeric virus vector of claim 7, wherein the insertion is an insertion of threonine.

### Claim 9 (depends on 1)

The chimeric virus vector of claim 1, wherein the chimeric virus vector comprises a chimeric AAV3b capsid comprising an amino acid insertion immediately following amino acid position 264 in an AAV3b capsid subunit having the amino acid sequence of (SEQ ID NO:15).

### Claim 10 (depends on 9)

The chimeric virus vector of claim 9, wherein the insertion is an insertion of threonine.

### Claim 11 (depends on 1)

The chimeric virus vector of claim 1, wherein the chimeric virus vector further comprises a selective amino acid substitution selected from the group consisting of:
(a) an amino acid substitution at amino acid position 263 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AAV capsid subunit;
(b) an amino acid substitution at amino acid position 450 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AVV capsid subunit;
(c) an amino substitution at amino acid position 457 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AVV capsid subunit; and
(d) any combination of (a) to (c) above.

### Claim 12 (depends on 11)

The chimeric virus vector of claim 11, wherein the chimeric virus vector comprises a chimeric AAV2 capsid comprising an amino acid substitution at amino acid position 263 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3).

### Claim 13 (depends on 12)

The chimeric virus vector of claim 12, wherein the substitution is a substitution of alanine for glutamine.

### Claim 14 (depends on 11)

The chimeric virus vector of claim 11, wherein the chimeric virus vector comprises a chimeric AAV3b capsid comprising an amino acid substitution at amino acid position 263 in the AAV3b capsid subunit having the amino acid sequence of (SEQ ID NO:15).

### Claim 15 (depends on 14)

The chimeric virus vector of claim 14, wherein the substitution is a substitution of alanine for glutamine.

### Claim 16 (depends on 11)

The chimeric virus vector of claim 11, wherein the chimeric virus vector comprises a chimeric AAV2 capsid comprising an amino acid substitution at amino acid position 450 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3).

### Claim 17 (depends on 16)

The chimeric virus vector of claim 16, wherein the substitution is a substitution of asparagine for threonine.

### Claim 18 (depends on 11)

The chimeric virus vector of claim 11, wherein the chimeric virus vector comprises a chimeric AAV2 capsid comprising an amino acid substitution at amino acid position 457 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3).

### Claim 19 (depends on 18)

The chimeric virus vector of claim 18, wherein the substitution is a substitution of asparagine for glutamine.

### Claim 20

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising:
(i) a selective amino acid substitution of an alanine for glutamine at amino acid position 263 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3);
(ii) a selective amino acid insertion of a threonine immediately following amino acid position 264 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3);
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 21

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising:
(i) a selective amino acid substitution of alanine for glutamine at amino acid position 263 in an AAV3b capsid subunit having the amino acid sequence of (SEQ ID NO:15);
(ii) a selective amino acid insertion of a threonine immediatly following amino acid position 264 in the AAV3b capsid subunit having the amino acid sequence of (SEQ ID NO:15);
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 22

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid substitution at amino acid position 450 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AVV capsid subunit;
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 23 (depends on 22)

The chimeric virus vector of claim 22, wherein the substitution is a substitution of asparagine for threonine.

### Claim 24

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid substitution at amino acid position 457 in an AAV2 capsid subunit having the amino acid sequence of(SEQ ID NO:3) or a corresponding change in another AVV capsid subunit;
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 25 (depends on 24)

The chimeric virus vector of claim 24, wherein the substitution is a substitution of asparagine for glutamine.

### Claim 26 (depends on 24)

The chimeric virus vector of claim 24, wherein the chimeric virus vector further comprises a selective amino acid substitution at amino acid position 450 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AAV the capsid subunit.

### Claim 27

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising:
(i) a selective amino acid insertion immediately following amino acid position 264 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AAV capsid subunit;
(ii) a selective amino acid substitution at amino acid position 263 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AAV the capsid subunit;
(iii) a selective amino acid substitution at amino acid position 705 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AAV the capsid subunit;
(iv) a selective amino substitution at amino acid position 708 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AVV the capsid subunit; and
(v) a selective amino substitution at amino acid position 716 in the AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3) or a corresponding change in another AVV the capsid subunit; and
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 28

A chimeric virus vector comprising,
(a) a chimeric adeno-associated virus (AVV) capsid comprising:
(i) a threonine insertion immediately following amino acid position 264 in an AAV2 capsid subunit(s) having the amino acid sequence of (SEQ ID NO:3);
(ii) an alanine for glutamine substitution at amino acid position 263 in the AAV2 capsid subunit(s) having the amino acid sequence of (SEQ ID NO:3);
(iii) an alanine for asparagine substitution at amino acid position 705 in the AAV2 capsid subunit(s) having the amino acid sequence of (SEQ ID NO:3);
(iv) an alanine for valine substitution at amino acid position 708 in the AAV2 capsid subunit(s) having the amino acid sequence of (SEQ ID NO:3); and
(v) an asparagine for threonine substitution at amino acid position 716 in the AAV2 capsid subunit(s) having the amino acid sequence of (SEQ ID NO:3).

### Claim 29 (depends on 1)

The chimeric virus vector of claim 1, wherein the insertion immediately following amino acid position 264 or corresponding change is present in all subunits of the AAV capsid.

### Claim 30 (depends on 1)

The chimeric virus vector of claim 1, wherein the heterologous nucleic acid sequence encodes a polypeptide.

### Claim 31 (depends on 30)

The chimeric virus vector of claim 30, wherein the polypeptide is a therapeutic polypeptide.

### Claim 32 (depends on 31)

The chimeric virus vector of claim 31, wherein the therapeutic polypeptide is selected from the group consisting of: dystrophin, mini-dystrophin, utrophin, a clotting factor including Factor VIII or Factor IX, a growth factor including insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, epidermal derived growth factor, fibroblast-derived growth factor, nerve-derived growth factor, glial-derived growth factor, transforming growth factor-α or transforming growth factor-β, a neurotrophic factor, an anti-inflammatory factor including transforming growth factor-α soluble receptor or IRAP, α1-antitrypsin, lysosomal acid-α glucosidase, β-glucocerebrosidase, α-galactosidase A, a cytokine, an interferon including β-interferon, TRAIL, FAS-ligand, endostatin, angiostatin, cystic fibrosis transmembrane regulator protein, erythropoietin, LDL receptor, lipoprotein lipase, ornithine transcarbamylase, β-globin, α-globin, spectrin, adenosine deaminase, hypoxanthine guanine phosphoribosyl transferase, sphingomyelinase, lysosomal hexosaminidase, branched-chain keto acid dehydrogenase, a bone morphogenic protein including VEGF and RANKL, protein phosphatase inhibitor I, phospholamban, serca2a, catalase, tyrosine hydroxylase, superoxide dismutase, leptin, RP65 protein, galanin, α-L-iduronidase, a hormone including insulin or somatotropin, galactocerebrosidase, phenylalanine hydroxylase, LDL receptor,soluble CD4, anti-apoptotic gene products, glutamate receptor, a lymphokine, barkct, β2-adrenergic receptor, calsarcin, enos, inos, a sarcoglycan, Fc receptor, T cell receptor, ApoE, ApoC, a suicide gene product, a tumor suppressor gene product, and any combination thereof.

### Claim 33 (depends on 1)

The chimeric virus vector of claim 1, wherein the heterologous nucleic acid sequence encodes an untranslated RNA.

### Claim 34 (depends on 33)

The chimeric virus vector of claim 33, wherein the untranslated RNA is an antisense RNA or an interfering RNA (RNAi).

### Claim 35 (depends on 33)

The chimeric virus vector of claim 33, wherein the untranslated RNA is directed to VEGF, the multiple drug resistance gene product, myostatin, or repeats in the Huntington Disease gene product.

### Claim 36 (depends on 1)

A composition comprising the chimeric virus vector according to claim 1.

### Claim 37 (depends on 1)

The chimeric virus vector of claim 1, wherein the insertion is an insertion of aspartic acid into the capsid subunit.

### Claim 38 (depends on 1)

The chimeric virus vector of claim 1, wherein the insertion is an insertion of glutamic acid into the capsid subunit.

### Claim 39 (depends on 1)

The chimeric virus vector of claim 1, wherein the insertion is an insertion of phenylalanine into the capsid subunit.

### Claim 40

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid insertion of aspartic acid immediately following amino acid position 264 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3); and
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 41

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid insertion of glutamic acid immediately following amino acid position 264 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3); and
(b) a nucleic acid comprising an AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 42

A chimeric virus vector comprising:
(a) a chimeric adeno-associated virus (AAV) capsid comprising a selective amino acid insertion of phenylalanine immediately following amino acid position 264 in an AAV2 capsid subunit having the amino acid sequence of (SEQ ID NO:3); and
(b) a nucleic acid comprising and AAV terminal repeat sequence and a heterologous nucleic acid sequence;
wherein the nucleic acid is packaged within the chimeric AAV capsid.

### Claim 43 (depends on 40)

The chimeric virus vector of claim 40, wherein the heterologous nucleic acid sequence encodes a polypeptide.

### Claim 44 (depends on 43)

The chimeric virus vector of claim 43, wherein the polypeptide is a therapeutic polypeptide.

### Claim 45 (depends on 44)

The chimeric virus vector of claim 44, wherein the therapeutic polypeptide is selected from the group consisting of: dystrophin, mini-dystrophin, utrophin, a clotting factor including Factor VII or Factor IX, a growth factor including insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, epidermal derived growth factor, fibroblast-derived growth factor, nerve-derived growth factor, glial-derived growth factor, transforming growth factor-α or transforming growth factor-β, a neurotrophic factor, an anti-inflammatory factor including transforming growth factor-α soluble receptor or IRAP, α1-antitrypsin, lysosomal acid-α glucosidase, β-glucocerebrosidase, α-galactosidase A, a cytokine, an interferon including β-interferon, TRAIL, FAS-ligand, endostatin, angiostatin, cystic fibrosis transmembrane regulator protein, erythropoietin, LDL receptor, lipoprotein lipase, ornithine transcarbamylase, β-globin, α-globin, spectrin, adenosine deaminase, hypoxanthine guanine phosphoribosyl transferase, sphingomyelinase, lysosomal hexosaminidase, branched-chain keto acid dehydrogenase, a bone morphogenic protein including VEGF and RANKL, protein phosphatase inhibitor I, phospholamban, serca2a, catalase, tyrosine hydroxylase, superoxide dismutase, leptin, RP65 protein, galanin, α-L-iduronidase, a hormone including insulin or somatotropin, galactocerebrosidase, phenylalanine hydroxylase, LDL receptor, soluble CD4, anti-apoptotic gene products, glutamate receptor, a lymphokine, barkct, β2-adrenergic receptor, calsarcin, enos, inos, a sarcoglycan, Fc receptor, T cell receptor, ApoE, ApoC, a suicide gene product, a tumor suppressor gene product, and any combination thereof.

### Claim 46 (depends on 40)

The chimeric virus vector of claim 40, wherein the heterologous nucleic acid sequence encodes an untranslated RNA.

### Claim 47 (depends on 46)

The chimeric virus vector of claim 46, wherein the untranslated RNA is an antisense RNA of an interfering RNA (RNAi).

### Claim 48 (depends on 46)

The chimeric virus of claim 46, wherein the untranslated RNA is directed to VEGF, the multiple drug resistance gene product, myostatin, or repeats in the Huntington Disease gene product.

### Claim 49 (depends on 40)

A composition comprising the chimeric virus vector according to claim 40.

### Claim 50 (depends on 41)

The chimeric virus vector of claim 41, wherein the heterologous nucleic acid sequence encodes a polypeptide.

### Claim 51 (depends on 50)

The chimeric virus vector of claim 50, wherein the polypeptide is a therapeutic polypeptide.

### Claim 52 (depends on 51)

The chimeric virus vector of claim 51, wherein the therapeutic polypeptide is selected from the group consisting of: dystrophin, mini-dystrophin, utrophin, a clotting factor including Factor VIII or Factor IX, a growth factor including insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, epidermal derived growth factor, fibroblast-derived growth factor, nerve-derived growth factor, glial-derived growth factor, transforming growth factor-α or transforming growth factor-β, a neurotrophic factor, an anti-inflammatory factor including transforming growth factor-α soluble receptor of IRAP, α1- antitrypsin, lysosomal acid-α glucosidase, β-glucocerebrosidase, α- galactosidase A, a cytokine, an interferon including β-interferon, TRAIL, FAS-ligand, endostatin, angiostatin, cystic fibrosis transmembrane regulator protein, erythropoietin, LDL receptor, lipoprotein lipase, ornithine transcarbamylase, β-globin, α-globin, spectrin, adenosine deaminase, hypoxanthine guanine phosphoribosyl transferase, sphingomyelinase, lysosomal hexosaminidase, branched-chain keto acid dehydrogenase, a bone morphogenic protein including VEGF and RANKL, protein phosphatase inhibitor I, phospholamban, serca2 a, catalase, tyrosine hydroxylase, superoxide dismutase, leptin, RP65 protein, galanin, α-L-iduronidase, a hormone including insulin or somatotropin, galactocerebrosidase, phenylalanine hydroxylase, LDL receptor, soluble CD4, anti-apoptotic gene products, glutamate receptor, a lymphokine, barkct, β2-adrenergic receptor, calsarcin, enos, inos, a sarcoglycan, Fc receptor, T cell receptor, ApoE, ApoC, a suicide gene product, a tumor suppressor gene product, and any combination thereof.

### Claim 53 (depends on 41)

The chimeric virus vector of claim 41, wherein the heterologous nucleic acid sequence encodes an untranslated RNA.

### Claim 54 (depends on 53)

The chimeric virus vector of claim 53, wherein the untranslated RNA is an antisense RNA or an interfering RNA (RNAi).

### Claim 55 (depends on 53)

The chimeric virus vector of claim 53, wherein the untranslated RNA is directed to VEGF, the multiple drug resistance gene product, myostatin, or repeats in the Huntington Disease gene product.

### Claim 56 (depends on 41)

A composition comprising the chimeric virus vector according to claim 41.

### Claim 57 (depends on 42)

The chimeric virus vector of claim 42, wherein the heterologous nucleic acid sequence encodes a polypeptide.

### Claim 58 (depends on 57)

The chimeric virus vector of claim 57, wherein the polypeptide is a therapeutic polypeptide.

### Claim 59 (depends on 58)

The chimeric virus vector of claim 58, wherein the therapeutic polypeptide is selected from the group consisting of: dystrophin, mini-dystrophin, utrophin, a clotting factor including Factor VIII or Factor IX, a growth factor including insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, epidermal derived growth factor I, insulin-like growth II, platelet-derived growth factor, epidermal derived growth factor, fibroblast-derived growth factor, nerve-derived growth factor, glial-derived growth factor, transforming growth factor-α or transforming growth factor-β, a neurotrophic factor, an anti-inflammatory factor including transforming growth factor-α soluble receptor of IRAP, α1-antitrypsin, lysosomal acid-α glucosidase, β-glucocerebrosidase, α-galactosidase A, a cytokine, an interferon including β-interferon, TRAIL, FAS-ligand, endostatin, angiostatin, cystic fibrosis transmembrane regulator protein, erythropoietin, LDL receptor, lipoprotein lipase, ornithine transcarbamylase, β-globin, α-globin, spectrin, adenosine deaminase, hypoxanthine guanine phosphoribosyl transferase, sphingomyelinase, lysosomal hexosaminidase, branched-chain keto acid dehydrogenase, a bone morphogenic protein including VEGF and RANKL, protein phosphatase inhibitor I, phospholamban, serca2a, catalase, tyrosine hydroxylase, superoxide dismutase, leptin, RP65 protein, galanin, α-L-iduronidase, a hormone including insulin or somatotropin, galactocerebrosidase, phenylalanine hydroxylase, LDL receptor, soluble CD4, anti-apoptotic gene products, glutamate receptor, a lymphokine, barkct, β2-adrenergic receptor, calsarcin, enos, inos, a sarcoglycan, Fc receptor, T cell receptor, ApoE, ApoC, a suicide gene product, a tumor suppressor gene product, and any combination thereof.

### Claim 60 (depends on 42)

The chimeric virus vector of claim 42, wherein the heterologous nucleic acid sequence encodes an untranslated RNA.

### Claim 61 (depends on 60)

The chimeric virus vector of claim 60, wherein the untranslated RNA is an antisense RNA or an interfering RNA (RNAi).

### Claim 62 (depends on 60)

The chimeric virus vector of claim 60, wherein the untranslated RNA is directed to VEGF, the multiple drug resistance gene product, myostatin, or repeats in the Huntington Disease gene product.

### Claim 63 (depends on 42)

A composition the chimeric virus vector according to claim 42.

### Claim 64 (depends on 1)

The chimeric virus vector of claim 1, wherein the selective amino acid insertion is an insertion of less than 12 contiguous amino acids.

### Claim 65 (depends on 1)

The chimeric virus vector of claim 1, wherein the selective amino acid insertion is an insertion of less than 4 contiguous amino acids.

### Claim 66 (depends on 1)

The chimeric virus vector of claim 1, wherein the selective amino acid insertion is an insertion of one amino acid.