Vectors, airway gene transfer

Fajac, I., Alio, J.-C., Souil, E., Merten, M., Pichon, C., Figarella, C. et al. (2000) Flistidylated polylysine as a synthetic vector for gene transfer into cystic fibrosis airway surface and airway gland serous cells. J. Gene Med., 2, 368-378. 

Kollen, W.J.W., Midoux, P., Erbacher, P., Yip, A., Roche, A.C., Monsigny, M. et al. (1996) Gluconoylated and glycosylated polylysines as vectors for gene transfer into cystic fibrosis airway epithelial cells. Hum. Gene Then, 7, 1577-1586. 

Wang, G., Sinn, P. L. and McCray, P. B., Jr. (2000). Development of retroviral vectors for gene transfer to airway epithelia. Curr. Opin. Mol. Ther. 2, 497-506. 

Johnson LG, Olsen JC, Naldini L, Boucher RC. Pseudotyped human lentiviral vector-mediated gene transfer to airway epithelia in vivo. Gene Ther 2000 7(7) 568-574. 

Ohkawara Y, Xing Z, Gauldie J, Jordana M. Adenovirus vector-mediated gene transfer of murine IL-10 inhibits antigen-induced airways inflammation in sensitized mice. Am J Respir Crit Care Med 1996 153 A143. 

B. Vector-Specific Barriers to Luminai Airway Gene Transfer... 

The lack of cell proliferation in WD airway epithelia in vivo (109) and low titers have traditionally served as major barriers to application of the C-type retroviral vectors derived from MLV to in vivo airway gene transfer efforts. The development of HIV, EIAV, and FIV vectors (103,104,106,108,110,111), which can transduce nondividing airway cells, may overcome the requirement for cell proliferation by oncogenic retroviruses (112). Advances in retroviral production techniques and pseudotyping of vectors to create stable envelopes that permit concentration of vector stocks may also soon overcome the limitations of titer (113). However, titers of retroviruses remain l-2 logs lower than that of Ad vectors. 

Respiratory syncytial vims is another member of the Paramyxoviridae family of viruses that has been considered for new vector development. RS V mediates cell entry through its glycoproteins G and F (215). Like SeV, transcription and replication are cystoplasmic events. In preliminary studies, a replication-competent RSV-GFP virus eflSciently transduced WD FIAE cells following apical, but not basolateial, application of vector (203). RS V will likely have similar limitations as SeV for vector development. However, SeV and RSV offer exciting promise for future human airway gene transfer efforts. 

Piedimonte G, Pickles RJ, Lehmaim JR, McCarty D, Costa DL, Boucher RC. Replication-deficient adenoviral vector for gene transfer potentiates airway neurogenic inflammation. Am J RespirCell Mol Biol 1997 16 250-258. 

Wang G, SiimPL, McCray PB, Jr. Developmentofretroviral vectors for gene transfer to airway epithelia. CurrOpin Mol Ther2000 2 497-506. 

Scanlin TF. Gluconoylated and glycosylated polylysines as vectors for gene transfer into cystic fibrosis airway epithelial cells. Hum GeneTher 1996 7 1577-1586. 

Answer Aerosol delivery of the CFTR gene. Both viruses and liposome-DNA complexes are capable of successful CFTR gene transfer to the nasal and airway epithelia of patients with CF. In fact, gene transfer to the airways is one of the few areas where liposome-DNA complexes match the expression obtained using viral vectors without the viruses inflammatory side effects. Current trials are aimed at optimizing gene delivery with reduced toxicity to produce sustained correction of the epithelial transport defect. 

Zabner J, ChUlon M, Granst T, Moninger TO, Davidson BL, Gregory R, Armentano D (1999) A chimeric type 2 adenovirus vector with a type 17 fiber enhances gene transfer to human airway epithelia. J Virol 73 8689-8695. 

Pickles RJ, McCarty D, Matsui H, Hart PJ, Randell SH, Boucher RC. Limited entry of adenovirus vectors into well-differentiated airway epithelium is responsible for inefficient gene transfer. J Virol 1998, 72, 6014-6023. 

Weiss D. Delivery of gene transfer vectors to lung obstacles and the role of adjunct techniques for airway administration. Mol Ther 2002 6(2) 148 152. 

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