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Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors.

Publication ,  Journal Article
Koeberl, DD; Alexander, IE; Halbert, CL; Russell, DW; Miller, AD
Published in: Proc Natl Acad Sci U S A
February 18, 1997

We previously found that gene transduction by adeno-associated virus (AAV) vectors in cell culture can be stimulated over 100-fold by treatment of the target cells with agents that affect DNA metabolism, such as irradiation or topoisomerase inhibitors. Here we show that previous gamma-irradiation increased the transduction rate in mouse liver by up to 900-fold, and the topoisomerase inhibitor etoposide increased transduction by about 20-fold. Similar rates of hepatic transduction were obtained by direct injection of the liver or by systemic delivery via tail vein injection. Hepatocytes were much more efficiently transduced than other cells after systemic delivery, and up to 3% of all hepatocytes could be transduced after one vector injection. The presence of wild-type AAV, which contaminates many AAV vector preparations, was required to observe a full response to gamma-irradiation. Injection of mice with AAV vectors encoding human clotting factor IX after gamma-irradiation resulted in synthesis of low levels of human clotting factor IX for the 5-month period of observation. These studies show the potential of targeted gene transduction of the liver by AAV vectors for treatment of various hematological or metabolic diseases.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 18, 1997

Volume

94

Issue

4

Start / End Page

1426 / 1431

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Topoisomerase I Inhibitors
  • Recombinant Proteins
  • Rats
  • Mice
  • Liver
  • Injections, Intravenous
  • Humans
  • Genetic Vectors
  • Genetic Therapy
 

Citation

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Koeberl, D. D., Alexander, I. E., Halbert, C. L., Russell, D. W., & Miller, A. D. (1997). Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors. Proc Natl Acad Sci U S A, 94(4), 1426–1431. https://doi.org/10.1073/pnas.94.4.1426
Koeberl, D. D., I. E. Alexander, C. L. Halbert, D. W. Russell, and A. D. Miller. “Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors.Proc Natl Acad Sci U S A 94, no. 4 (February 18, 1997): 1426–31. https://doi.org/10.1073/pnas.94.4.1426.
Koeberl DD, Alexander IE, Halbert CL, Russell DW, Miller AD. Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1426–31.
Koeberl, D. D., et al. “Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors.Proc Natl Acad Sci U S A, vol. 94, no. 4, Feb. 1997, pp. 1426–31. Pubmed, doi:10.1073/pnas.94.4.1426.
Koeberl DD, Alexander IE, Halbert CL, Russell DW, Miller AD. Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1426–1431.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 18, 1997

Volume

94

Issue

4

Start / End Page

1426 / 1431

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Topoisomerase I Inhibitors
  • Recombinant Proteins
  • Rats
  • Mice
  • Liver
  • Injections, Intravenous
  • Humans
  • Genetic Vectors
  • Genetic Therapy