Skip to main content
Journal cover image

Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation

Publication ,  Conference
Kesseli, SJ; Krischak, MK; Gao, Q; Gonzalez, T; Zhang, M; Halpern, SE; Kahan, R; Song, M; Huffman, N; Xu, H; Abraham, N; Asokan, A ...
Published in: Journal of Thoracic and Cardiovascular Surgery
July 1, 2023

Objective: Adeno-associated virus is a clinically used gene therapy vector but has not been studied in lung transplantation. We sought to determine the efficacy of adeno-associated virus delivery during static cold storage via the airway versus the pulmonary artery before lung transplantation in a rodent model. Methods: Lewis rat lung grafts were treated with a dose of 8e8 or 4e9 viral genome/μL recombinant adeno-associated virus subtype-9 vectors containing firefly luciferase genomes administered via the pulmonary artery or airway during cold storage. A control group did not receive adeno-associated virus. Recipient syngeneic rats then underwent single left lung transplantation. Animals underwent bioluminescence imaging on postoperative days 7, 14, 28, and 56. Explanted tissues were prepared as lysates to quantify luciferase activity. Immunohistochemistry was performed to evaluate cellular transgene expression patterns. Results: Control animals with no luminescent signal produced a background radiance of 6.1e4 p/s/cm2/sr. In the airway delivery group, mean radiance was greater than the control at 4e9 viral genome/μL postoperative day 7 radiance 6.9e4 p/s/cm2/sr (P = .04). In the pulmonary artery delivery group, we observed greater in vivo luminescence in animals receiving 4e9 viral genome/μL compared with all other groups. However, analysis of tissue lysate revealed greater luminescence in the airway delivery group and suggested off-target expression in heart and liver tissue in the pulmonary artery delivery group. Immunohistochemistry demonstrated transgene staining in distal airway epithelium and alveoli but sparing of the vasculature in the airway delivery group. Conclusions: Adeno-associated virus mediates gene transduction during static cold storage in rat lung isografts when administered via the airway and pulmonary artery. Airway administration leads to robust transgene expression in respiratory epithelial cells, whereas pulmonary artery administration targets alternative cell types and increases extrapulmonary transgene expression.

Duke Scholars

Published In

Journal of Thoracic and Cardiovascular Surgery

DOI

EISSN

1097-685X

ISSN

0022-5223

Publication Date

July 1, 2023

Volume

166

Issue

1

Start / End Page

e38 / e49

Related Subject Headings

  • Respiratory System
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kesseli, S. J., Krischak, M. K., Gao, Q., Gonzalez, T., Zhang, M., Halpern, S. E., … Hartwig, M. G. (2023). Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation. In Journal of Thoracic and Cardiovascular Surgery (Vol. 166, pp. e38–e49). https://doi.org/10.1016/j.jtcvs.2022.08.050
Kesseli, S. J., M. K. Krischak, Q. Gao, T. Gonzalez, M. Zhang, S. E. Halpern, R. Kahan, et al. “Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation.” In Journal of Thoracic and Cardiovascular Surgery, 166:e38–49, 2023. https://doi.org/10.1016/j.jtcvs.2022.08.050.
Kesseli SJ, Krischak MK, Gao Q, Gonzalez T, Zhang M, Halpern SE, et al. Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation. In: Journal of Thoracic and Cardiovascular Surgery. 2023. p. e38–49.
Kesseli, S. J., et al. “Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation.” Journal of Thoracic and Cardiovascular Surgery, vol. 166, no. 1, 2023, pp. e38–49. Scopus, doi:10.1016/j.jtcvs.2022.08.050.
Kesseli SJ, Krischak MK, Gao Q, Gonzalez T, Zhang M, Halpern SE, Kahan R, Song M, Huffman N, Xu H, Abraham N, Asokan A, Barbas AS, Hartwig MG. Adeno-associated virus mediates gene transduction after static cold storage treatment in rodent lung transplantation. Journal of Thoracic and Cardiovascular Surgery. 2023. p. e38–e49.
Journal cover image

Published In

Journal of Thoracic and Cardiovascular Surgery

DOI

EISSN

1097-685X

ISSN

0022-5223

Publication Date

July 1, 2023

Volume

166

Issue

1

Start / End Page

e38 / e49

Related Subject Headings

  • Respiratory System
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology