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Persistent, therapeutically relevant levels of human granulocyte colony-stimulating factor in mice after systemic delivery of adeno-associated virus vectors.

Publication ,  Journal Article
Koeberl, DD; Bonham, L; Halbert, CL; Allen, JM; Birkebak, T; Miller, AD
Published in: Hum Gene Ther
September 1, 1999

Adeno-associated virus (AAV) vectors have been shown to preferentially transduce hepatocytes after systemic administration in adult mice and to provide long-term expression of introduced genes. One application of this technology would be for the production of granulocyte colony-stimulating factor (G-CSF), which increases mature neutrophil numbers in humans and in animals, and has therapeutic effects in disorders featuring chronic neutropenia, including cyclic, severe congenital, and idiopathic neutropenia, and glycogen storage disease type Ib. We have treated mice by tail vein injection of AAV vectors encoding human G-CSF, and have detected high G-CSF levels and marked elevation of neutrophil counts for at least 5 months. A therapeutically relevant amount of G-CSF production was obtained when the liver-specific mouse albumin promoter-enhancer was used to drive G-CSF expression. In mice receiving higher amounts of vector, plasma levels of human G-CSF gradually increased over 3 weeks to high concentrations, whereas for lower amounts human G-CSF remained at initial, low levels. The previously observed effect of gamma irradiation, to increase AAV transduction rates, was diminished when large amounts of vector were used. Absolute neutrophil counts increased 10- to 50-fold for the period of observation to levels that would be therapeutic in the treatment of cyclic neutropenia. In conclusion, gene therapy with AAV vectors synthesizing G-CSF shows promise for the treatment of disorders featuring neutropenia.

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Published In

Hum Gene Ther

DOI

ISSN

1043-0342

Publication Date

September 1, 1999

Volume

10

Issue

13

Start / End Page

2133 / 2140

Location

United States

Related Subject Headings

  • Recombinant Proteins
  • Neutrophils
  • Mice, Inbred C57BL
  • Mice
  • Liver
  • Humans
  • Granulocyte Colony-Stimulating Factor
  • Genetic Vectors
  • Gene Transfer Techniques
  • Gamma Rays
 

Citation

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Koeberl, D. D., Bonham, L., Halbert, C. L., Allen, J. M., Birkebak, T., & Miller, A. D. (1999). Persistent, therapeutically relevant levels of human granulocyte colony-stimulating factor in mice after systemic delivery of adeno-associated virus vectors. Hum Gene Ther, 10(13), 2133–2140. https://doi.org/10.1089/10430349950017121
Koeberl, D. D., L. Bonham, C. L. Halbert, J. M. Allen, T. Birkebak, and A. D. Miller. “Persistent, therapeutically relevant levels of human granulocyte colony-stimulating factor in mice after systemic delivery of adeno-associated virus vectors.Hum Gene Ther 10, no. 13 (September 1, 1999): 2133–40. https://doi.org/10.1089/10430349950017121.
Koeberl DD, Bonham L, Halbert CL, Allen JM, Birkebak T, Miller AD. Persistent, therapeutically relevant levels of human granulocyte colony-stimulating factor in mice after systemic delivery of adeno-associated virus vectors. Hum Gene Ther. 1999 Sep 1;10(13):2133–40.
Koeberl, D. D., et al. “Persistent, therapeutically relevant levels of human granulocyte colony-stimulating factor in mice after systemic delivery of adeno-associated virus vectors.Hum Gene Ther, vol. 10, no. 13, Sept. 1999, pp. 2133–40. Pubmed, doi:10.1089/10430349950017121.
Koeberl DD, Bonham L, Halbert CL, Allen JM, Birkebak T, Miller AD. Persistent, therapeutically relevant levels of human granulocyte colony-stimulating factor in mice after systemic delivery of adeno-associated virus vectors. Hum Gene Ther. 1999 Sep 1;10(13):2133–2140.
Journal cover image

Published In

Hum Gene Ther

DOI

ISSN

1043-0342

Publication Date

September 1, 1999

Volume

10

Issue

13

Start / End Page

2133 / 2140

Location

United States

Related Subject Headings

  • Recombinant Proteins
  • Neutrophils
  • Mice, Inbred C57BL
  • Mice
  • Liver
  • Humans
  • Granulocyte Colony-Stimulating Factor
  • Genetic Vectors
  • Gene Transfer Techniques
  • Gamma Rays