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Adeno-associated viral vectors based on serotype 3b use components of the fibroblast growth factor receptor signaling complex for efficient transduction.

Publication ,  Journal Article
Messina, EL; Nienaber, J; Daneshmand, M; Villamizar, N; Samulski, J; Milano, C; Bowles, DE
Published in: Hum Gene Ther
October 2012

Adeno-associated virus type 3b (AAV3b) has been largely ignored by gene therapists because of the inability of vectors based on this serotype to transduce target tissues efficiently. Here we describe a phenomenon unique to AAV3b in that vectors based on this serotype mediate enhanced transduction in the presence of heparin. Among the many biological functions attributed to heparin, its interaction with, and ability to regulate, several growth factors (GFs) and growth factor receptors (GFRs) has been well characterized. Using GFR-overexpressing cell lines, soluble GFs and heparins, as well as specific GFR inhibitors, we have demonstrated a requirement for fibroblast growth factor receptor-2 (FGFR2) and FGF1 in the heparin-mediated augmentation of AAV3b vector transduction. In contrast to AAV2, we establish that heparin can be used as an adjunct with AAV3b to further increase transduction in a variety of cells and target tissues, additionally suggesting that AAV3b may be an attractive viral vector for clinical use during procedures in which heparin is used. In summary, AAV3b exhibits FGFR2-dependent, markedly enhanced transduction efficiency in the presence of heparin and FGFs, which could make it a useful vector for gene therapy in a variety of human diseases.

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Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

October 2012

Volume

23

Issue

10

Start / End Page

1031 / 1042

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • Tissue Culture Techniques
  • Sus scrofa
  • Solubility
  • Serotyping
  • Saphenous Vein
  • Receptor, Fibroblast Growth Factor, Type 2
  • Mice
  • Luciferases
  • Intercellular Signaling Peptides and Proteins
 

Citation

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Messina, E. L., Nienaber, J., Daneshmand, M., Villamizar, N., Samulski, J., Milano, C., & Bowles, D. E. (2012). Adeno-associated viral vectors based on serotype 3b use components of the fibroblast growth factor receptor signaling complex for efficient transduction. Hum Gene Ther, 23(10), 1031–1042. https://doi.org/10.1089/hum.2012.066
Messina, Emily L., Jeffrey Nienaber, Mani Daneshmand, Nestor Villamizar, Jude Samulski, Carmelo Milano, and Dawn E. Bowles. “Adeno-associated viral vectors based on serotype 3b use components of the fibroblast growth factor receptor signaling complex for efficient transduction.Hum Gene Ther 23, no. 10 (October 2012): 1031–42. https://doi.org/10.1089/hum.2012.066.
Messina EL, Nienaber J, Daneshmand M, Villamizar N, Samulski J, Milano C, et al. Adeno-associated viral vectors based on serotype 3b use components of the fibroblast growth factor receptor signaling complex for efficient transduction. Hum Gene Ther. 2012 Oct;23(10):1031–42.
Messina, Emily L., et al. “Adeno-associated viral vectors based on serotype 3b use components of the fibroblast growth factor receptor signaling complex for efficient transduction.Hum Gene Ther, vol. 23, no. 10, Oct. 2012, pp. 1031–42. Pubmed, doi:10.1089/hum.2012.066.
Messina EL, Nienaber J, Daneshmand M, Villamizar N, Samulski J, Milano C, Bowles DE. Adeno-associated viral vectors based on serotype 3b use components of the fibroblast growth factor receptor signaling complex for efficient transduction. Hum Gene Ther. 2012 Oct;23(10):1031–1042.
Journal cover image

Published In

Hum Gene Ther

DOI

EISSN

1557-7422

Publication Date

October 2012

Volume

23

Issue

10

Start / End Page

1031 / 1042

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • Tissue Culture Techniques
  • Sus scrofa
  • Solubility
  • Serotyping
  • Saphenous Vein
  • Receptor, Fibroblast Growth Factor, Type 2
  • Mice
  • Luciferases
  • Intercellular Signaling Peptides and Proteins