Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 38; pp. 16363 - 16368
• Main Authors: Brantly, Mark L, Chulay, Jeffrey D, Wang, Lili, Mueller, Christian, Humphries, Margaret, Spencer, L. Terry, Rouhani, Farshid, Conlon, Thomas J, Calcedo, Roberto, Betts, Michael R, Spencer, Carolyn, Byrne, Barry J, Wilson, James M, Flotte, Terence R
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 22.09.2009; National Acad Sciences
• Subjects: Adeno-associated virus; Adeno-associated virus 1; Adult; Aged; alpha 1-Antitrypsin - blood; alpha 1-Antitrypsin - genetics; alpha 1-Antitrypsin - metabolism; alpha 1-Antitrypsin Deficiency - genetics; alpha 1-Antitrypsin Deficiency - therapy; Antibodies; Antibodies, Viral - blood; Biological Sciences; Blood; Capsid; Capsid - enzymology; Capsid - immunology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Line; Cells; Clinical trials; Dependovirus - genetics; Dependovirus - immunology; Enzyme linked immunosorbent assay; Enzymes; epididymitis; Female; Gene Expression; Gene therapy; gene transfer; Genetic Therapy - methods; Genetic vectors; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; genome; Genomics; hematology; Humans; immune response; Injection; Injections, Intramuscular; interferon-gamma; Lymphocytes; Male; Middle Aged; Neutralizing antibodies; patients; Recombinant Fusion Proteins - blood; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; serotypes; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Transgenes; Viruses

Alpha-1 antitrypsin (AAT) deficiency is well-suited as a target for human gene transfer. We performed a phase 1, open-label, dose-escalation clinical trial of a recombinant adeno-associated virus (rAAV) vector expressing normal (M) AAT packaged into serotype 1 AAV capsids delivered by i.m. injection...