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Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver
Open accessAbstract
Vectors based on adeno-associated virus (AAV) are effective in gene delivery in vivo. Tissue-specific gene expression is often needed to minimize ectopic expression in unintended cells and undesirable consequences. Here, we investigated whether incorporation of target sequences of tissue-specific microRNA (miRNA) into AAV vectors could inhibit ectopic expression in tissues such as the liver and hematopoietic cells. First we inserted liver-specific miR-122 target sequences (miR-122T) into the 3'-untranslated region (UTR) of a number of AAV vectors. After intravenous delivery in mice, we found that five copies of the 20mer miR-122T reduced liver expression of luciferase by 50-fold and β-galactosidase (LacZ) by 70-fold. Five copies of miR-122T also reduced mRNA levels of a secretable protein (myostatin propeptide) from the AAV vector plasmid by 23-fold in the liver. However, gene expression in other tissues, including the heart was not inhibited. Similarly, we inserted four copies of miR-142-3pT or miR-142-5pT, both hematopoietic lineage-specific, into the 3'-UTR of the AAV-luciferase vector. We wished to see whether they could prolong transgene expression by inhibiting expression in antigen-presenting cells. However, in vivo luciferase gene expression in major tissues declined with time, regardless of the miR-142 target sequences used. Quantitative analysis of the vector DNA in various tissues revealed that the decline of transgene expression in vivo was mainly because of promoter shut-off other than loss of AAV-transduced cells by immune destruction. Moreover, transgene expression was not detected in circulating mononuclear cells after delivering AAV9 vector with or without miR142T. These results demonstrate that liver-specific miR-122 target sequence in AAV vectors was highly efficient in reducing liver expression, whereas hematopoietic miR-142 target sequences were ineffective in preventing decline of AAV vector gene expression in nonhematopoietic tissues resulted from promoter shut-off.
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“Incorporation of 5 copies of miR-122 target sequences has shown enhanced inhibitory effects over 3 copies in the liver of ICR mice, while without any significant change in transduction efficiency in 293 T cells [33].”
From Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside (2024) · cites this paper as [33]
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Identification of Novel Genes Coding for Small Expressed RNAs
Lagos-Quintana, M., Rauhut, R., Lendeckel, W., & Tuschl, T. (2001) · Science · doi:10.1126/science.1064921 · Cited by 4,956
Mammalian microRNAs predominantly act to decrease target mRNA levels
Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010) · Nature · doi:10.1038/nature09267 · Cited by 3,886
Manno, C. S., Pierce, G. F., Arruda, V. R., Glader, B., Ragni, M., Rasko, J. J. E., Ozelo, M. C., Hoots, K., Blatt, P., Konkle, B., et al. (2006) · Nature Medicine · doi:10.1038/nm1358 · Cited by 2,163
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145
Xiao, X., Li, J., & Samulski, R. J. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2224-2232.1998 · Cited by 1,381
Self-citationKaplitt, M. G., Feigin, A., Tang, C., Fitzsimons, H. L., Mattis, P., Lawlor, P. A., Bland, R. J., Young, D., Strybing, K., Eidelberg, D., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60982-9 · Cited by 1,067
Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., et al. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.107 · Cited by 954
Gene therapy using adeno-associated virus vectors
Daya, S., & Berns, K. I. (2008) · Clinical Microbiology Reviews · doi:10.1128/cmr.00008-08 · Cited by 926
Xiao, X., Li, J., & Samulski, R. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.8098-8108.1996 · Cited by 913
Self-citationMaguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G.-S., Rossi, S., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61836-5 · Cited by 865
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Metadata
- Authors
- Qiao, C., Yuan, Z., Li, J., He, B., Zheng, H., Mayer, C., Li, J., & Xiao, X.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Qiao, C
- Xiao, X
- ORCID
- He, B
- Venue
- Gene Therapy
- Published
- 2010-12-09
- Volume
- 18
- Issue
- 4
- Pages
- 403-410
- ISSN
- 0969-7128 (ISSN-L)
- 1476-5462
- PMC
- PMC3686499
- OpenAlex
- W2086500311
- Cited by
- 163
- References
- 62
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 16 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 8 · 2019: 9 · 2018: 7 · 2017: 10 · 2016: 6 · 2015: 12 · 2014: 11 · 2013: 11 · 2012: 8
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR45967, R01AR045967, AR 56394, R01AR056394)
- 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 › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- adeno-associated virus vectors, miR-122, miR-142, 3' untranslated region, liver-specific gene expression, tissue-specific gene expression, ectopic expression, hematopoietic cells, AAV9, myostatin propeptide, intravenous gene delivery
- MeSH terms
- Dependovirus, Animals, Antigen-Presenting Cells, beta-Galactosidase, Gene Expression Regulation, Genetic Vectors, Liver, Luciferases, Organ Specificity, Gene Transfer Techniques, Transgenes, MicroRNAs, Mice, Myostatin
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