Quantitative analysis of the packaging capacity of recombinant adeno-associated virus
Abstract
Recombinant adeno-associated viruses (AAV) are among the most promising vectors for gene therapy of genetic diseases, including cystic fibrosis (CF). However, because of its small genome size, the capacity of AAV to package a therapeutic gene is limited. The efficiency of packaging the cystic fibrosis transmembrane conductance Regulator (CFTR) gene into AAV will be an important factor in determining whether recombinant AAV can be developed as a vector for transferring CFTR cDNA to the airway epithelia of patients with CF. Current understanding of the AAV biology suggests that AAV can package a genome slightly larger than the size of a wild-type genome. The precise range of the genome size and the efficiency of packaging have not been defined. Using a series of AAV vectors with progressively increasing genome size, we were able to analyze quantitatively the packaging efficiency in relation to the vector size and to determine the size limit for packaging. The packaging efficiencies of AAV vectors of variable sizes were determined directly by assaying DNA contents of viral particles, and indirectly by analyzing their efficiency in transfer of a chloramphenicol acetyltransferase (CAT) reporter gene into target cells. Our studies showed that the optimal size of AAV vector is between 4.1 and 4.9 kb. Although AAV can package a vector larger than its genome size, up to 5.2 kb, the packaging efficiencies in this large size range were sharply reduced. When the AAV genome size was smaller than 4.1 kb, the packaging efficiency was also suboptimal. In contrast, when the size of the genome was less than half the length of the wild-type genome, two copies of the vector were packaged into each virion, suggesting that the copy number control during packaging is a “head-full” mechanism. Because the length of the minimal cDNA of CFTR is about 4.5 kb, these results suggest it is possible to package the CFTR gene into AAV if the combined length of transcriptional elements and ITRs is kept under 500 bp. The results of this study are important for directing the design of AAV vectors for efficient gene transfer, as well as for a better understanding of the mechanism of AAV genome packaging. Adeno-associated virus (AAV) has been engineered as vectors to express genes of interest. The genome size of wild-type AAV is 4.6 kb. The total of size of the AAV vector influences the efficiency of its packaging into AAV virions. We have quantitatively determined the relationship of vector size to packaging efficiency by constructing 12 AAV vectors of different lengths. These vectors vary from 2 kb to 6 kb in size and carry a chloramphenicol acetyltransferase (CAT) reporter gene. The packaging efficiencies of these vectors were determined both by quantitating the DNA content of viral particles and assaying the efficiency of AAV virions in transferring CAT gene into HeLa cells. The results of our study demonstrate that the packaging efficiency of AAV is greatly affected by the length of the genome. AAV can package vectors ranging from 2 to 5.2 kb in size, but the optimal vector length for packaging is between 4.1 and 4.9 kb.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The AAV vector system has a small DNA packaging limit (4.7-5 kb), which motivates the use of small recombinant promoters.
“The major restriction of the system is the small DNA packaging limit of 4.7 kb (Dong et al., 1996).”
From Recombinant Human Myelin-Associated Glycoprotein Promoter Drives Selective AAV-Mediated Transgene Expression in Oligodendrocytes (2016) · cites this paper as Dong et al., 1996
AAV has a strict size cutoff of 5.2 kb.
“other studies [6-8] indicated that intact genomes were not, in fact, packaged in that case [3], and further suggested a strict size cutoff of 5.2 kb.”
From Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons (2014) · cites this paper as [3]
AAV vectors have a relatively small maximal packaging capacity.
“However, the use of AAV vectors is limited by their relatively small maximal packaging capacity [3,4].”
From Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons (2014) · cites this paper as [3]
Dong et al. generated packaging constructs containing a completely recombinant genome encoding the chloramphenicol acetyltransferase gene, ranging in size from 1,918 to 6,019 bp.
“Dong et al. generated packaging constructs, containing a completely recombinant genome encoding the chloramphenicol acetyltransferase (CAT) gene, ranging in size from 1,918 to 6,019 bp (10).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [10]
The latter studies suggest that the optimum size of AAV2 vector genomes is between 4.1 and 4.9 kb.
“The latter studies suggest that the optimum size of AAV2 vector genomes is between 4.1 and 4.9 kb.”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [10]
AAV vectors larger than 5.2 kb are packaged very inefficiently, and their transduction efficiencies are dramatically reduced.
“vectors larger than 5.2 kb were found to be packaged very inefficiently, and transduction efficiencies of these oversized vectors were dramatically reduced. 26”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [26]
The optimum packaging size for AAV genomes is between 4.1 and 4.9 kb.
“The optimum packaging size for genomes was determined to be between 4.1 and 4.9 kb”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [26]
rAAVs can package genomes ranging from 2 to 5.2 kb in size.
“Dong et al. 26 reported that rAAVs can package genomes ranging from 2 to 5.2 kb in size.”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [26]
Cites
Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA
Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., et al. (1989) · Science · doi:10.1126/science.2475911 · Cited by 7,418 · see citing works
Basic Methods in Molecular Biology
(1986) · Elsevier eBooks · doi:10.1016/b978-0-444-01082-7.x5001-2 · Cited by 3,163 · see citing works
Site-specific integration by adeno-associated virus.
Kotin, R. M., Siniscalco, M., Samulski, R. J., Zhu, X. D., Hunter, L., Laughlin, C. A., McLaughlin, S., Muzyczka, N., Rocchi, M., & Berns, K. I. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.6.2211 · Cited by 906 · see citing works
Targeted integration of adeno‐associated virus (AAV) into human chromosome 19.
Samulski, R. J., Zhu, X., Xiao, X., Brook, J. D., Housman, D. E., Epstein, N., & Hunter, L. A. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04964.x · Cited by 783 · see citing works
Use of Adeno-Associated Virus as a General Transduction Vector for Mammalian Cells
Muzyczka, N. (1992) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-75608-5_5 · Cited by 756 · see citing works
Nucleotide sequence and organization of the adeno-associated virus 2 genome
Srivastava, A., Lusby, E. W., & Berns, K. I. (1983) · Journal of Virology · doi:10.1128/jvi.45.2.555-564.1983 · Cited by 721 · see citing works
Fisher, K. J., Gao, G. P., Weitzman, M. D., DeMatteo, R. P., Burda, J. F., & Wilson, J. M. (1996) · Journal of Virology · doi:10.1128/jvi.70.1.520-532.1996 · Cited by 546 · see citing works
HOGGAN, M. D., Blacklow, N. R., & Rowe, W. P. (1966) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.55.6.1467 · Cited by 540 · see citing works
Flotte, T. R., Afione, S. A., Conrad, C., McGrath, S. A., Solow, R., Oka, H., Zeitlin, P. L., Guggino, W. B., & Carter, B. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10613 · Cited by 490 · see citing works
Hermonat, P. L., & Muzyczka, N. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.20.6466 · Cited by 480 · see citing works
Construction of plasmids that expressE.coli β-galactosidase in mammalian cells
MacGregor, G. R., & Caskey, C. T. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.6.2365 · Cited by 458 · see citing works
Comparison of Intron-Dependent and Intron-Independent Gene Expression
Buchman, A. R., & Berg, P. R. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.10.4395-4405.1988 · Cited by 370 · see citing works
Adeno-associated virus general transduction vectors: analysis of proviral structures
McLaughlin, S. K., Collis, P., Hermonat, P. L., & Muzyczka, N. (1988) · Journal of Virology · doi:10.1128/jvi.62.6.1963-1973.1988 · Cited by 348 · see citing works
Flotte, T. R., Afione, S. A., Solow, R., Drumm, M. L., Markakis, D., Guggino, W. B., Zeitlin, P. L., & Carter, B. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53762-5 · Cited by 342 · see citing works
Samulski, R. J., Srivastava, A., Berns, K. I., & Muzyczka, N. (1983) · Cell · doi:10.1016/0092-8674(83)90342-2 · Cited by 297 · see citing works
Cloning of infectious adeno-associated virus genomes in bacterial plasmids
Laughlin, C. A., Tratschin, J.-D., Coon, H., & Carter, B. J. (1983) · Gene · doi:10.1016/0378-1119(83)90217-2 · Cited by 266 · see citing works
Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors
Podsakoff, G. M., Wong, K. K., & Chatterjee, S. S. (1994) · Journal of Virology · doi:10.1128/jvi.68.9.5656-5666.1994 · Cited by 233 · see citing works
Berns, K. I. (1990) · Microbiological Reviews · doi:10.1128/mr.54.3.316-329.1990 · Cited by 232 · see citing works
Characterization of the DNA of a defective human parvovirus isolated from a genital site
Bantel‐Schaal, U., & Hausen, H. Z. (1984) · Virology · doi:10.1016/0042-6822(84)90271-x · Cited by 188 · see citing works
Positive and negative autoregulation of the adeno-associated virus type 2 genome
Labow, M., Hermonat, P. L., & Berns, K. I. (1986) · Journal of Virology · doi:10.1128/jvi.60.1.251-258.1986 · Cited by 187 · see citing works
Berns, K. I. (1990) · Microbiological Reviews · doi:10.1128/mmbr.54.3.316-329.1990 · Cited by 163 · see citing works
Adeno-associated virus vectors
Carter, B. J. (1992) · Current Opinion in Biotechnology · doi:10.1016/0958-1669(92)90082-t · Cited by 160 · see citing works
Deletion of the E4 region of the genome produces adenovirus DNA concatemers.
Weiden, M. D., & Ginsberg, H. S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.1.153 · Cited by 150 · see citing works
LEBKOWSKI, J. S., McNally, M. A., OKARMA, T. B., & Lerch, L. B. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.10.3988-3996.1988 · Cited by 137 · see citing works
A cascade of adenovirus early functions is required for expression of adeno-associated virus
Richardson, W. D. (1981) · Cell · doi:10.1016/0092-8674(81)90367-6 · Cited by 120 · see citing works
Ruffing, M., Zentgraf, H., & Kleinschmidt, J. A. (1992) · Journal of Virology · doi:10.1128/jvi.66.12.6922-6930.1992 · Cited by 109 · see citing works
Tounekti, N., Mougel, M., Roy, C., Marquet, R., Darlix, J., Paoletti, J., Ehresmann, B., & Ehresmann, C. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90726-z · Cited by 101 · see citing works
Recombinant junctions formed by site-specific integration of adeno-associated virus into an episome
Giraud, C., Winocour, E., & Berns, K. I. (1995) · Journal of Virology · doi:10.1128/jvi.69.11.6917-6924.1995 · Cited by 92 · see citing works
Labow, M., & Berns, K. I. (1988) · Journal of Virology · doi:10.1128/jvi.62.5.1705-1712.1988 · Cited by 57 · see citing works
Richardson, W. D., & Westphal, H. (1984) · Journal of Virology · doi:10.1128/jvi.51.2.404-410.1984 · Cited by 49 · see citing works
Regulation of adeno-associated virus DNA replication
Berns, K. I., Kotin, R. M., & Labow, M. (1988) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/0167-4781(88)90116-9 · Cited by 36 · see citing works
Expression and rescue of a nonselected marker from an integrated AAV vector
Mendelson, E., Smith, M. G., & Carter, B. J. (1988) · Virology · doi:10.1016/0042-6822(88)90157-2 · Cited by 24 · see citing works
Flagged first, then by citations
Research works printed but not linked: 22
- I., 1989, J. Vkol., 63, 4450
- P., 1968, J. Nad. Cancer Inst., 40, 319
- FERRARI F., 1996, J. Vkol., 70, 3227
- GIRAUD C, 1995, J. Vkol., 69, 6917
- P., 1966, Proc. Nafl. Acad. Sci. U S A, 55, 1457
- IM D.S., 1989, J. Vkol., 63, 3095
- LEVER A.M., 1996, J. Vkol., 70, 880
- KOTIN R.M., 1992, E M B O J., 11, 5071
- BERNS K.I., 1986, J. Vkol., 60, 215
- COLLIS P., 1988, J. Vkol., 62, 1963
- N., 1988, J. Vkol., 62, 1963
- SMITH M.G., 1988, Vkology, 166, 154
- CARRIERE C., 1995, Vkology, 213, 1
- N., 1992, Curr. Topics Microbiol. Immunol., 158, 97
- CARTER B.J., 1980, Vkology, 102, 71
- JR, 1994, J. Vkol., 68, 5656
- PREVEC L., 1989, Gen. Vkol., 70, 2539
- RICHARDSON W.D., 1984, J. Vkol., 51, 404
- RUFFING M., 1992, J. Vkol., 66, 6922
- SAMULSKI R.J., 1989, J. Vkol., 63, 3822
- SAMULSKI R.J., 1991, E M B O J., 10, 3941
- SRIVASTAVA A., 1983, J. Vkol., 45, 555
Cited by
Sorted by citations
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444 · see citing works
Optogenetics in neural systems
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M., & Deisseroth, K. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.004 · Cited by 1,881 · see citing works
Base editing: precision chemistry on the genome and transcriptome of living cells
Rees, H. A., & Liu, D. R. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0059-1 · Cited by 1,675 · see citing works
In vivo gene editing in dystrophic mouse muscle and muscle stem cells
Tabebordbar, M., Zhu, K., Cheng, J. K. W., Chew, W. L., Widrick, J. J., Yan, W. X., Maesner, C., Wu, E. Y., Xiao, R., Ran, F. A., et al. (2016) · Science · doi:10.1126/science.aad5177 · Cited by 1,046 · see citing works
Effect of genome size on AAV vector packaging
Wu, Z., Yang, H., & Colosi, P. (2010) · Molecular Therapy · doi:10.1038/mt.2009.255 · Cited by 1,025 · see citing works
Therapeutic in vivo gene transfer for genetic disease using AAV: Progress and challenges
Mingozzi, F., & High, K. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2988 · Cited by 893 · see citing works
McCarty, D., Monahan, P., & Samulski, R. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301514 · Cited by 735 · see citing works
High, K. A., & Roncarolo, M. G. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1706910 · Cited by 555 · see citing works
Directed evolution of adeno-associated virus yields enhanced gene delivery vectors
Maheshri, N., Koerber, J. T., Kaspar, B. K., & Schaffer, D. V. (2006) · Nature Biotechnology · doi:10.1038/nbt1182 · Cited by 538 · see citing works
Self-complementary AAV vectors; advances and applications
McCarty, D. M. (2008) · Molecular Therapy · doi:10.1038/mt.2008.171 · Cited by 515 · see citing works
Grieger, J. C., & Samulski, R. J. (2005) · Journal of Virology · doi:10.1128/jvi.79.15.9933-9944.2005 · Cited by 419 · see citing works
Keeler, A. M., & Flotte, T. R. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015530 · Cited by 322 · see citing works
Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.110 · Cited by 306 · see citing works
Loeb, J. E., Cordier, W. S., Harris, M. E., Weitzman, M. D., & Hope, T. J. (1999) · Human Gene Therapy · doi:10.1089/10430349950016942 · Cited by 279 · see citing works
Intracellular transport of recombinant adeno-associated virus vectors
Nonnenmacher, M., & Weber, T. (2012) · Gene Therapy · doi:10.1038/gt.2012.6 · Cited by 258 · see citing works
Characterization of Genome Integrity for Oversized Recombinant AAV Vector
Dong, B., Nakai, H., & Xiao, W. (2010) · Molecular Therapy · doi:10.1038/mt.2009.258 · Cited by 230 · see citing works
Intravitreal injection of AAV2 transduces macaque inner retina
Yin, L., Greenberg, K., Hunter, J. J., Dalkara, D., Kolstad, K. D., Masella, B. D., Wolfe, R., Visel, M., Stone, D., Libby, R. T., et al. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.10-6250 · Cited by 212 · see citing works
Immune responses to adeno-associated virus and its recombinant vectors.
Sun, J. Y., Anand-Jawa, V, Chatterjee, S., & Wong, K. K. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302039 · Cited by 215 · see citing works
AAV Capsid Structure and Cell Interactions
Agbandje-McKenna, M., & Kleinschmidt, J. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-61779-370-7_3 · Cited by 215 · see citing works
Choi, J.-H., Yu, N.-K., Baek, G.-C., Bakes, J., Seo, D., Nam, H. J., Baek, S. H., Lim, C.-S., Lee, Y.-S., & Kaang, B.-K. (2014) · Molecular Brain · doi:10.1186/1756-6606-7-17 · Cited by 197 · see citing works
Gene delivery to the eye using adeno-associated viral vectors
Martin, K. R. G., Klein, R. L., & Quigley, H. A. (2002) · Methods · doi:10.1016/s1046-2023(02)00232-3 · Cited by 149 · see citing works
Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids
Chamberlain, K., Riyad, J. M., & Weber, T. (2016) · Human Gene Therapy Methods · doi:10.1089/hgtb.2015.140 · Cited by 141 · see citing works
Adeno-Associated Virus Gene Therapy for Liver Disease
Kattenhorn, L. M., Tipper, C. H., Stoica, L., Geraghty, D. S., Wright, T. L., Clark, K. R., & Wadsworth, S. C. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.160 · Cited by 138 · see citing works
Design and Packaging of Adeno-Associated Virus Gene Targeting Vectors
Hirata, R. K., & Russell, D. W. (2000) · Journal of Virology · doi:10.1128/jvi.74.10.4612-4620.2000 · Cited by 133 · see citing works
Glial promoter selectivity following AAV-delivery to the immature brain
von Jonquieres, G., Mersmann, N., Klugmann, C. B., Harasta, A. E., Lutz, B., Teahan, O., Housley, G. D., Fröhlich, D., Krämer-Albers, E.-M., & Klugmann, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065646 · Cited by 133 · see citing works
Monahan, P. E., Lothrop, C. D., Sun, J., Hirsch, M. L., Kafri, T., Kantor, B., Sarkar, R., Tillson, D. M., Elia, J. R., & Samulski, R. J. (2010) · Molecular Therapy · doi:10.1038/mt.2010.170 · Cited by 125 · see citing works
Methods for Gene Transfer to the Central Nervous System
Kantor, B., Bailey, R. M., Wimberly, K., Kalburgi, S. N., & Gray, S. J. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00003-2 · Cited by 109 · see citing works
Pañeda, A., Vanrell, L., Mauleon, I., Crettaz, J. S., Berraondo, P., Timmermans, E. J., Beattie, S. G., Twisk, J., van Deventer, S., Prieto, J., et al. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.031 · Cited by 109 · see citing works
Tools for efficient genome editing; ZFN, TALEN, and CRISPR
Shamshirgaran, Y., Liu, J., Sumer, H., Verma, P. J., & Taheri-Ghahfarokhi, A. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2301-5_2 · Cited by 114 · see citing works
Ghosh, A., Yue, Y., & Duan, D. (2011) · Human Gene Therapy · doi:10.1089/hum.2010.122 · Cited by 95 · see citing works
Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20
McCraw, D. M., O’Donnell, J. K., Taylor, K. A., Stagg, S. M., & Chapman, M. S. (2012) · Virology · doi:10.1016/j.virol.2012.05.004 · Cited by 84 · see citing works
Understanding Capsid Assembly and Genome Packaging for Adeno-Associated Viruses
Bennett, A., Mietzsch, M., & Agbandje-McKenna, M. (2017) · Future Virology · doi:10.2217/fvl-2017-0011 · Cited by 82 · see citing works
Gene therapy for retinal disease
McClements, M. E., & MacLaren, R. E. (2013) · Translational Research · doi:10.1016/j.trsl.2012.12.007 · Cited by 80 · see citing works
Schnödt, M., & Büning, H. (2017) · Human Gene Therapy Methods · doi:10.1089/hgtb.2016.188 · Cited by 77 · see citing works
rAAV-compatible MiniPromoters for restricted expression in the brain and eye
de Leeuw, C. N., Korecki, A. J., Berry, G. E., Hickmott, J. W., Lam, S. L., Lengyell, T. C., Bonaguro, R. J., Borretta, L. J., Chopra, V., Chou, A. Y., et al. (2016) · Molecular Brain · doi:10.1186/s13041-016-0232-4 · Cited by 76 · see citing works
Grose, W. E., Clark, K. R., Griffin, D., Malik, V., Shontz, K. M., Montgomery, C. L., Lewis, S., Brown, R. H., Janssen, P. M. L., Mendell, J. R., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039233 · Cited by 76 · see citing works
Ghosh, A., Yue, Y., & Duan, D. (2006) · The Journal of Gene Medicine · doi:10.1002/jgm.835 · Cited by 69 · see citing works
von Jonquieres, G., Fröhlich, D., Klugmann, C. B., Wen, X., Harasta, A. E., Ramkumar, R., Spencer, Z. H. T., Housley, G. D., & Klugmann, M. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00013 · Cited by 60 · see citing works
“…Georg von Jonquieres, Dominik Fröhlich, Claudia B. Klugmann, Xin Wen, Anne E. Harasta, Roshini Ramkumar, Ziggy H. T. Spencer, Gary D. Housley and Matthias Klugmann* Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, UNSW Australia, Sydney, NSW,…”
BackgroundInfluentialOligonucleotide conjugated multi-functional adeno-associated viruses
Katrekar, D., Moreno, A. M., Chen, G., Worlikar, A., & Mali, P. (2018) · Scientific Reports · doi:10.1038/s41598-018-21742-x · Cited by 57 · see citing works
Xu, Z., Yue, Y., Lai, Y., Ye, C., Qiu, J., Pintel, D. J., & Duan, D. (2004) · Human Gene Therapy · doi:10.1089/hum.2004.15.896 · Cited by 55 · see citing works
Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery
Joshi, C. R., Labhasetwar, V., & Ghorpade, A. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-016-9724-3 · Cited by 55 · see citing works
Approaches to gene modulation therapy for ALS
Meijboom, K. E., & Brown, R. H. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01285-w · Cited by 38 · see citing works
Lai, Y., Yue, Y., Liu, M., & Duan, D. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.1036 · Cited by 37 · see citing works
A novel retinal ganglion cell promoter for utility in AAV vectors
Hanlon, K. S., Chadderton, N., Palfi, A., Blanco Fernandez, A., Humphries, P., Kenna, P. F., Millington-Ward, S., & Farrar, G. J. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00521 · Cited by 34 · see citing works
Library Selection and Directed Evolution Approaches to Engineering Targeted Viral Vectors
Jang, J., Lim, K., & Schaffer, D. V. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21541 · Cited by 26 · see citing works
Kagiava, A., Sargiannidou, I., Bashiardes, S., Richter, J., Schiza, N., Christodoulou, C., Gritti, A., & Kleopa, K. A. (2014) · The Journal of Gene Medicine · doi:10.1002/jgm.2813 · Cited by 12 · see citing works
- Authors
- Dong, J.-Y., Fan, P.-D., & Frizzell, R. A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Dong, Jian-Yun
- ORCID
- Frizzell, Raymond A.
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 1996-11-10
- Volume
- 7
- Issue
- 17
- Pages
- 2101-2112
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W2051442157
- Semantic Scholar
- 8084d1cef626b24406cdffe2668a4e46c1c8cf70
- Cited by
- 583
- References
- 32
- Citations by year
- 2026: 29 · 2025: 26 · 2024: 40 · 2023: 32 · 2022: 31 · 2021: 25 · 2020: 29 · 2019: 22 · 2018: 21 · 2017: 19 · 2016: 11 · 2015: 21 · 2014: 10 · 2013: 16 · 2012: 21
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cystic Fibrosis Foundation
- National Institutes of Health (5r01hl046177-03, 5p30dk047766-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-47766, DK58029, R01 DK/HL46177)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- adeno-associated virus, adeno-associated virus vectors, cystic fibrosis, CFTR gene, copy number control, inverted terminal repeats, chloramphenicol acetyltransferase reporter, gene therapy vectors, double-stranded DNA
- MeSH terms
- Dependovirus, Cells, Cultured, Cloning, Molecular, DNA, Viral, Genetic Vectors, HeLa Cells, Humans, Recombination, Genetic, Transfection, Blotting, Southern, Chloramphenicol O-Acetyltransferase, Genome, Viral, Genes, Reporter, Gene Transfer Techniques, Virus Assembly
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
