Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function?

Roberta M. Lassance; Caroline P. Pássaro; Sabrina V. Martini; Raquel C. Castiglione; Tatiana M. Gutierrez; Soraia C. Abreu; Mariana A. Antunes; Debora G. Xisto; Liudmila Cebotaru; Hilda Petrs-Silva; Walter A. Zin; William B. Guggino; Rafael Linden; Patricia R.M. Rocco; Marcelo M. Morales

doi:10.1016/j.resp.2007.09.002

Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function?

Roberta M. Lassance, Caroline P. Pássaro, Sabrina V. Martini, Raquel C. Castiglione, Tatiana M. Gutierrez, Soraia C. Abreu, Mariana A. Antunes, Debora G. Xisto, Liudmila Cebotaru, Hilda Petrs-Silva, Walter A. Zin, William B. Guggino, Rafael Linden, Patricia R.M. Rocco, Marcelo M. Morales

School of Medicine

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Forty-eight BALB/c mice were divided into two groups of 24 animals each. In the control group (CTRL) saline was intratracheally instilled, while the virus group (VR) received rAAV2-GFP (4 × 10⁹ particles). These groups were subdivided into four sub-groups (n = 6). Pulmonary mechanical parameters were analyzed after 3 weeks (VR1d3w) and at 1 (VR2d1w), 2 (VR2d2w) and 3 weeks (VR2d3w) after a second AAV2 dose. Fractions of the area of alveolar collapse and the amount of polymorpho- and mononuclear cells were determined by point-counting technique. Viral transduction was evaluated by immunohistochemistry. Lung mechanical data were similar in all groups. However, there was an increase in airway and lung parenchyma cellularity and in the fraction of area of alveolar collapse in the VR2d2w group, which nonetheless decreased with time. There was no evidence of apoptosis in any group. In conclusion, the gene transfer vector AAV2 induces, in the lung, a discrete inflammatory reaction that does not affect either baseline lung mechanics or airway hyperresponsiveness.

Original language	English (US)
Pages (from-to)	91-98
Number of pages	8
Journal	Respiratory Physiology and Neurobiology
Volume	160
Issue number	1
DOIs	https://doi.org/10.1016/j.resp.2007.09.002
State	Published - Jan 1 2008

Keywords

Adeno-associated virus type 2
Gene therapy
Pulmonary mechanics
Vector

ASJC Scopus subject areas

General Neuroscience
Physiology
Pulmonary and Respiratory Medicine

Access to Document

10.1016/j.resp.2007.09.002

Cite this

Lassance, R. M., Pássaro, C. P., Martini, S. V., Castiglione, R. C., Gutierrez, T. M., Abreu, S. C., Antunes, M. A., Xisto, D. G., Cebotaru, L., Petrs-Silva, H., Zin, W. A., Guggino, W. B., Linden, R., Rocco, P. R. M., & Morales, M. M. (2008). Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function? Respiratory Physiology and Neurobiology, 160(1), 91-98. https://doi.org/10.1016/j.resp.2007.09.002

Lassance, RM, Pássaro, CP, Martini, SV, Castiglione, RC, Gutierrez, TM, Abreu, SC, Antunes, MA, Xisto, DG, Cebotaru, L, Petrs-Silva, H, Zin, WA, Guggino, WB, Linden, R, Rocco, PRM & Morales, MM 2008, 'Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function?', Respiratory Physiology and Neurobiology, vol. 160, no. 1, pp. 91-98. https://doi.org/10.1016/j.resp.2007.09.002

@article{ea926bc451fd4f8c93a441a9bc050814,

title = "Does the use of recombinant AAV2 in pulmonary gene therapy damage lung function?",

abstract = "Forty-eight BALB/c mice were divided into two groups of 24 animals each. In the control group (CTRL) saline was intratracheally instilled, while the virus group (VR) received rAAV2-GFP (4 × 109 particles). These groups were subdivided into four sub-groups (n = 6). Pulmonary mechanical parameters were analyzed after 3 weeks (VR1d3w) and at 1 (VR2d1w), 2 (VR2d2w) and 3 weeks (VR2d3w) after a second AAV2 dose. Fractions of the area of alveolar collapse and the amount of polymorpho- and mononuclear cells were determined by point-counting technique. Viral transduction was evaluated by immunohistochemistry. Lung mechanical data were similar in all groups. However, there was an increase in airway and lung parenchyma cellularity and in the fraction of area of alveolar collapse in the VR2d2w group, which nonetheless decreased with time. There was no evidence of apoptosis in any group. In conclusion, the gene transfer vector AAV2 induces, in the lung, a discrete inflammatory reaction that does not affect either baseline lung mechanics or airway hyperresponsiveness.",

keywords = "Adeno-associated virus type 2, Gene therapy, Pulmonary mechanics, Vector",

author = "Lassance, {Roberta M.} and P{\'a}ssaro, {Caroline P.} and Martini, {Sabrina V.} and Castiglione, {Raquel C.} and Gutierrez, {Tatiana M.} and Abreu, {Soraia C.} and Antunes, {Mariana A.} and Xisto, {Debora G.} and Liudmila Cebotaru and Hilda Petrs-Silva and Zin, {Walter A.} and Guggino, {William B.} and Rafael Linden and Rocco, {Patricia R.M.} and Morales, {Marcelo M.}",

note = "Funding Information: The authors would like to express their gratitude to Mr. Antonio Carlos de Souza Quaresma, Mr. Andre Benedito da Silva, and Mrs. Jaqueline Lima do Nascimento for their skillful technical assistance. This work was supported by Funda{\c c}{\~a}o Jos{\'e} Bonif{\'a}cio de (FUJB), Funda{\c c}{\~a}o Carlos Chagas Filho de Amparo {\`a} Pesquisa do Estado do Rio de Janeiro (FAPERJ), Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (FAPESP), Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico (CNPq), Centers of Excellence Program (PRONEX-MCT, PRONEX-FAPERJ), and Gene Therapy Millennium Institute-CNPq. The authors are members of the Millenium Institute-Gene Therapy Network (MCT/CNPq, Brazil).",

year = "2008",

month = jan,

day = "1",

doi = "10.1016/j.resp.2007.09.002",

language = "English (US)",

volume = "160",

pages = "91--98",

journal = "Respiratory Physiology and Neurobiology",

issn = "1569-9048",