The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene
Open accessAbstract
Adenoviral (Ad)-mediated in vivo gene transfer and expression are limited in part by cellular immune responses to viral-encoded proteins and/or transgene immunogenicity. In an attempt to diminish the former responses, we have previously developed and described helper-dependent (HD) Ad vectors in which the viral protein coding sequences are completely eliminated. These HD vectors have up to 37 kb insert capacity, are easily propagated in a Cre recombinase-based system, and can be produced to high concentration and purity (>99.9% helper-free vector). In this study, we compared safety and efficacy of leptin gene delivery mediated by an HD vector (HD-leptin) and a first-generation E1-deleted Ad vector (Ad-leptin) in normal lean and ob/ob (leptin-deficient) mice. In contrast to evidence of liver toxicity, inflammation, and cellular infiltration observed with Ad-leptin delivery in mice, HD-leptin delivery was associated with a significant improvement in associated safety/toxicity and resulted in efficient gene delivery, prolonged elevation of serum leptin levels, and associated weight loss. The greater safety, efficient gene delivery, and increased insert capacity of HD vectors are significant improvements over current Ad vectors and represent favorable features especially for clinical gene therapy applications.
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Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Cited by
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Verma, I. M., & Weitzman, M. D. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.050304.091637 · Cited by 616
Morral, N., O’Neal, W., Rice, K., Leland, M., Kaplan, J., Piedra, P. A., Zhou, H., Parks, R. J., Velji, R., Aguilar-Córdova, E., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12816 · Cited by 409
Self-citationRegulatable gene expression systems for gene therapy applications: progress and future challenges
Goverdhana, S., Puntel, M., Xiong, W., Zirger, J. M., Barcia, C., Curtin, J. F., Soffer, E. B., Mondkar, S., King, G. D., Hu, J., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.03.022 · Cited by 283
Gene Therapy with Viral Vectors
Kootstra, N. A., & Verma, I. M. (2003) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.140257 · Cited by 267
Adenoviral Vector Immunity: Its Implications and Circumvention Strategies
S. Ahi, Y., S. Bangari, D., & K. Mittal, S. (2011) · Current Gene Therapy · doi:10.2174/156652311796150372 · Cited by 185
Metadata
- Authors
- Morsy, M. A., Gu, M., Motzel, S., Zhao, J., Lin, J., Su, Q., Allen, H., Franlin, L., Parks, R. J., Graham, F. L., Kochanek, S., Bett, A. J., & Caskey, C. T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-07-07
- Volume
- 95
- Issue
- 14
- Pages
- 7866-7871
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2114445152
- Cited by
- 365
- References
- 1
- FWCI
- 24.27
- Type
- journal article
- Language
- en
- Open access
- green
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- Morsy, M. A., Gu, M., Motzel, S., Zhao, J., Lin, J., Su, Q., Allen, H., Franlin, L., Parks, R. J., Graham, F. L., Kochanek, S., Bett, A. J., & Caskey, C. T. (1998). An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.14.7866
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