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chondrocytes in situ through direct injection. Many preclinical gene therapy studies 10 – 13 have utilized various viral vectors to deliver IL-1ra to joints by both in vitro and in vivo delivery mechanisms. In the earlier preclinical gene therapy studies

Full access
in Journal of the American Veterinary Medical Association

to human medicine, it continues to gain attention in veterinary medicine, with a recent review 5 identifying particular areas of gene therapy applications, including cardiovascular disease, ocular disease, neoplasia, skin disease, and blood

Open access
in American Journal of Veterinary Research

often signals the end of a horse's competitive career. Similar to the situation in humans, most osteoarthritis treatments in horses are targeted at ameliorating the signs of the disease and are not curative. Gene therapy is currently being investigated

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in American Journal of Veterinary Research

Gene therapy has been used experimentally in orthopedics for fracture repair, 1–5 vertebral column fusion, 6–10 treatment of arthritis, 11–18 and, in horses, for treatment of osteoarthritis. 19 Introduction of a gene into resident cells to

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in American Journal of Veterinary Research

Abstract

Objective—To characterize the biological effects of IM administration of a recombinant adeno-associated virus serotype 2 (rAAV2) vector containing feline erythropoietin (fEPO) cDNA and determine whether readministration of the vector or removal of muscle tissue at the injection sites alters those effects.

Animals—10 healthy 7-week-old specific pathogenfree cats.

Procedure—Cats received 1 × 107 infective units (iU; n = 3), 1 × 108 iU (3), or 1 × 109 iU (2) of rAAV2-fEPO vector IM (day 0). Two control cats received an rAAV2 vector containing the LacZ gene (1 × 109 iU, IM). In all cats, hematologic variables and serum fEPO concentration were measured at intervals; anti-rAAV2 antibody titer was measured on day 227. In cats that did not respond to treatment, the rAAV2- fEPO vector was readministered. Injection sites were subsequently surgically removed.

Results—Compared with control cats, cats treated with 1 × 109 iU of rAAV2-fEPO vector had increased Hct and serum fEPO concentrations. One of these cats developed pure RBC aplasia; its Hct normalized following injection site excision. Cats receiving lower doses of vector had no response; on retreatment, 1 of those cats developed sustained erythrocytosis that persisted despite injection site removal and the others did not respond or responded transiently. Antibodies against rAAV2 were detected in all vector-treated cats.

Conclusions and Clinical Relevance—Gene therapy may be an effective treatment for cats with hypoproliferative anemia. However, rAAV2-fEPO vector administration may result in pure RBC aplasia or pathologic erythrocytosis, and injection site removal does not consistently abolish the biological response. (Am J Vet Res 2005;66:450–456)

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in American Journal of Veterinary Research
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cell, neutrophil, T cell, B cell, and dendritic cell) inhibition, reduced proliferation, and prevention of cytokine and chemokine release ( Figure 4 ) . 53 The therapeutic use of AAV–HLA-G for ocular disease may be advantageous over other gene therapy

Open access
in American Journal of Veterinary Research

correct the underlying dysfunction. Use of a vector to replace a dysfunctional gene (ie, gene therapy) may allow correction of a genetic problem at its source. The purpose of the study reported here was to compare basal mitochondrial OCR and maximal

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in American Journal of Veterinary Research
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therapy, hematopoietic bone marrow transplants, and gene therapy. Mucopolysaccharidoses I and VI cause blindness primarily through the development of corneal opacities, a result of the buildup of intra- and extracellular glycosaminoglycans. Recently, gene

Open access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate aberrations of the p53 tumor suppressor gene in naturally developing tumors in dogs.

Sample Population—Tumor specimens from 15 dogs with various tumors, including malignant lymphoma (7 dogs), monocytic leukemia (1), mammary gland adenoma (1), mammary gland benign mixed tumor (1), rhabdomyosarcoma (1), colon cancer (1), and osteosarcoma (3).

Procedure—Aberrations of the p53 gene in these tumor tissues were examined by reverse transcriptase- polymerase chain reaction and single-strand conformation polymorphism analysis, using 3 fragments that covered the entire open reading frame of the canine p53 gene, followed by nucleotide sequencing of the abnormal bands.

Results—Point mutations, deletions, and insertions resulting in a number of amino acid substitutions of wild-type p53 were detected in 7 of the 15 tumor specimens from dogs with malignant lymphoma, monocytic leukemia, rhabdomyosarcoma, colon cancer, and osteosarcoma. Of these 7 dogs, 2 had aberrations of the p53 gene on both alleles, whereas 5 had aberrations of the p53 gene on 1 allele and concurrently lacked the wild-type p53 transcript. Many of the aberrations of the p53 gene detected in these tumors were located in the transactivation, DNA binding, and oligomerization domains.

Conclusions and Clinical Relevance—Various naturally developing tumors in dogs often have inactivation of the p53 tumor suppressor gene, which may be 1 of the multiple step-wise genetic changes during tumorigenesis. This study indicates that p53 gene can be a target for gene therapy for tumors in dogs. (Am J Vet Res 2001;62:433–439)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the nucleotide sequence of the α IIb gene from canine platelet-derived cDNA.

Animals—3 adult dogs.

Procedure—First-strand cDNA was prepared from total RNA isolated from canine platelets. The cDNA was amplified, using specific primers in polymerase chain reaction (PCR), and the nucleotide sequence was obtained from purified PCR products.

Results—Except for the nucleotide at position 694, results of all sequencing reactions of α IIb were identical for canine platelet-derived cDNA. Canine α IIb had 3 fewer codons than α IIb of humans. The nucleotide and deduced amino acid sequences of full-length canine α IIb shared ≥ 83% similarity with the sequences established for humans. Segments of canine α IIb nucleotide and deduced amino acid sequences were ≥ 78% similar to α IIb associated with 7 functional domains (extracellular, transmembrane, cytoplasmic, and 4 calcium-binding domains) in humans, with the highest degree of similarity correlating with the sequences of the 4 calcium-binding domains. Amino acid residues associated with development of alloantibodies in humans (Met837, Val837, Ile843, Ser843) are not encoded by canine α IIb .

Conclusions and Clinical Relevance—The nucleotide variation at position 694 of canine α IIb may represent a polymorphism. The species differences in the α IIb sequence may contribute to variations in receptor-li gand interactions. The high degree of α IIb sequence conservation of the 4 calcium-binding domains implies functional importance. Some disorders associated with α IIb β3 in dogs are clinically analogous to diseases in humans, and results indicate that dogs are an appropriate model for the evaluation of gene therapy and other treatments of platelet-associated disorders. (Am J Vet Res 2001;62:1486–1492)

Full access
in American Journal of Veterinary Research