The DOI matches its Crossref record; 19 of the 20 references it cites were found in a registry or an index.
Trans-splicing vectors expand the utility of adeno-associated virus for gene therapy
Open accessAbstract
Adeno-associated viral (AAV) vectors have demonstrated considerable promise for gene therapy of inherited diseases. However, with a packaging size of <5 kb, applications have been limited to relatively small disease genes. Based on the finding that AAV genomes undergo intermolecular circular concatamerization after transduction in muscle, we have developed a paradigm to increase the size of delivered transgenes with this vector through trans-splicing between two independent vectors coadministered to the same tissue. When two vectors encoding either the 5′ or 3′ portions of the erythropoietin genomic locus were used, functional erythropoietin protein was expressed in muscle subsequent to the formation of intermolecular circular concatamers in a head-to-tail orientation through trans-splicing between these two independent vector genomes. These findings will allow for the application of AAV technologies to a wider variety of diseases for which therapeutic transgenes exceed the packaging limitation of present AAV vectors.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“All of these methods require multiple vectors, and the efficiency of some of these methods is inherently limited by the efficiencies of intron processing or homologous recombination.”
From Effect of genome size on AAV vector packaging (2010) · cites this paper as [5]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Recently, split vector systems, exploiting head-to-tail concatamerization formation, have been developed to circumvent the small packaging capacity of AAV genomes (13-16, 41, 52).”
From Packaging Capacity of Adeno-Associated Virus Serotypes: Impact of Larger Genomes on Infectivity and Postentry Steps (2005) · cites this paper as [52]
The cited source says what the claim attributes to it.
In the citing paper
“The trans-splicing method to expand the size of ORFs that can be successfully expressed using AAV vectors was originally developed in the laboratory of John Engelhardt 52,53 and has since been utilized in several studies with varying success (e.g., refs. 53-57 ).”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [53]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Summerford, C., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.2.1438-1445.1998 · Cited by 1,409
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
αVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection
Summerford, C., Bartlett, J. S., & Samulski, R. J. (1999) · Nature Medicine · doi:10.1038/4768 · Cited by 711
Duan, D., Sharma, P., Yang, J., Yue, Y., Dudus, L., Zhang, Y., Fisher, K. J., & Engelhardt, J. F. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8568-8577.1998 · Cited by 522
Self-citationSamulski, R. J., Chang, L., & Shenk, T. E. (1987) · Journal of Virology · doi:10.1128/jvi.61.10.3096-3101.1987 · Cited by 449
Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2
Qing, K., Mah, C., Hansen, J., Zhou, S., Dwarki, V., & Srivastava, A. (1999) · Nature Medicine · doi:10.1038/4758 · Cited by 443
Animal Model of Adenine-Induced Chronic Renal Failure in Rats
Yokozawa, T., Zheng, P., Oura, H., & Koizumi, F. (2008) · The Nephron journals/Nephron journals · doi:10.1159/000183992 · Cited by 356
Biology of Adeno-associated Virus
Berns, K. I., & Giraud, C. (1996) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-80207-2_1 · Cited by 308
Clark, K. R., Liu, X., McGrath, J. P., & Johnson, P. R. (1999) · Human Gene Therapy · doi:10.1089/10430349950018427 · Cited by 306
Yang, J., Zhou, W., Zhang, Y., Zidon, T. M., Ritchie, T. L., & Engelhardt, J. F. (1999) · Journal of Virology · doi:10.1128/jvi.73.11.9468-9477.1999 · Cited by 201
Self-citation
Flagged first, then by citations
1 of the 20 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- N Muzyczka Curr Top Microbiol Immunol 158, 97–129 (1992).
- N Qu, J K Wen, E Li Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 15, 222–224 (1995).
- F Zhang, P Laneuville, R F Gagnon, B Morin, A G Brox Exp Hematol 24, 1469–1474 (1996).
Cited by
Sorted by citations
Items 301–304 of 304
Development of AAV vectors for the therapy of autoimmune and inflammatory diseases
Li, C., Hirsch, M. L., & Samulski, R. J. (2010) · Springer eBooks · doi:10.1007/978-3-0346-0165-8_11
Molecular Therapeutic Approaches for Myocardial Protection
Pachori, A. S., Melo, L. G., & Dzau, V. J. (2005) · Humana Press eBooks · doi:10.1385/1-59259-883-8:157
Sarkis, C., & Mallet, J. J. (2005) · Cambridge University Press eBooks · doi:10.1017/cbo9780511544873.023
Metadata
- Authors
- Yan, Z., Zhang, Y., Duan, D., & Engelhardt, J. F.
- Affiliations
- University of Iowa (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-06-06
- Volume
- 97
- Issue
- 12
- Pages
- 6716-6721
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC18714
- OpenAlex
- W2082328650
- Cited by
- 305
- References
- 20
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 5 · 2021: 12 · 2020: 12 · 2019: 14 · 2018: 9 · 2017: 10 · 2016: 7 · 2015: 11 · 2014: 9 · 2013: 14 · 2012: 7
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL058340, R01 HL58340)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK 54759, P30DK054759)
- 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
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Keywords
- adeno-associated virus vectors, trans-splicing, erythropoietin, gene therapy
- MeSH terms
- Dependovirus, Anemia, Animals, Erythropoietin, Genetic Vectors, Kidney Failure, Chronic, Mice, Inbred C57BL, Muscles, Genetic Therapy, Mice
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
