Mammalian Retrovirus-like Protein PEG10 Packages Its Own MRNA and Can Be Pseudotyped for MRNA Delivery
Open accessAbstract
Hitching a ride with a retroelement: Retroviruses and retroelements have inserted their genetic code into mammalian genomes throughout evolution. Although many of these integrated virus-like sequences pose a threat to genomic integrity, some have been retooled by mammalian cells to perform essential roles in development. Segel et al . found that one of these retroviral-like proteins, PEG10, directly binds to and secretes its own mRNA in extracellular virus–like capsids. These virus-like particles were then pseudotyped with fusogens to deliver functional mRNA cargos to mammalian cells. This potentially provides an endogenous vector for RNA-based gene therapy. —DJ
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SEND using modified PEG10 was adapted for mouse and human cell lines and showed up to 40% editing of the VEGFA gene in HEK cells.
“The SEND delivery, using the modified PEG10, was adapted for application in both mouse and human cell lines, and they showed up to 40% editing of the VEGFA gene in HEK cells.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [85]
SEND may have reduced immunogenicity compared to currently available viral vectors due to its use of endogenous human proteins.
“Immune responses have not been evaluated, but SEND may have reduced immunogenicity compared to currently available viral vectors due to its use of endogenous human proteins [85].”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [85]
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Cites
Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723 · see citing works
Pushko, P., Pumpens, P., & Grens, E. (2013) · Intervirology · doi:10.1159/000346773 · Cited by 5,970 · see citing works
A statistical model for identifying proteins by tandem mass spectrometry.
Nesvizhskii, A., Keller, A., Kolker, E., & Aebersold, R. (2003) · Analytical Chemistry · doi:10.1021/ac0341261 · Cited by 4,902 · see citing works
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex
Konermann, S., Brigham, M. D., Trevino, A. E., Joung, J., Abudayyeh, O. O., Barcena, C., Hsu, P. D., Habib, N., Gootenberg, J. S., Nishimasu, H., et al. (2015) · Nature · doi:10.1038/nature14136 · Cited by 2,825 · see citing works
Self-citationA Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core
Zimmermann, L., Stephens, A., Nam, S.-Z., Rau, D., Kübler, J., Lozajic, M., Gabler, F., Söding, J., Lupas, A. N., & Alva, V. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.12.007 · Cited by 2,522 · see citing works
Single-cell reconstruction of the early maternal–fetal interface in humans
Vento-Tormo, R., Efremova, M., Botting, R. A., Turco, M. Y., Vento-Tormo, M., Meyer, K. B., Park, J.-E., Stephenson, E., Polański, K., Goncalves, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0698-6 · Cited by 2,358 · see citing works
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
Platt, R. J., Chen, S., Zhou, Y., Yim, M. J., Swiech, L., Kempton, H. R., Dahlman, J. E., Parnas, O., Eisenhaure, T. M., Jovanovic, M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.014 · Cited by 2,001 · see citing works
Self-citationMolecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,847 · see citing works
Differential analysis of RNA-seq incorporating quantification uncertainty
Pimentel, H., Bray, N. L., Puente, S., Melsted, P., & Pachter, L. (2017) · Nature Methods · doi:10.1038/nmeth.4324 · Cited by 1,534 · see citing works
Shevchenko, A., Jensen, O. N., Podtelejnikov, A. V., Sagliocco, F. A., Wilm, M. S., Vorm, O., Mortensen, P. M., Shevchenko, A., Boucherie, H., & Mann, M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14440 · Cited by 1,429 · see citing works
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127 · see citing works
Massively parallel single-nucleus RNA-seq with DroNc-seq
Habib, N., Avraham-Davidi, I., Basu, A., Burks, T., Shekhar, K., Hofree, M., Choudhury, S. R., Aguet, F., Gelfand, E., Ardlie, K., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4407 · Cited by 1,069 · see citing works
Self-citationInterspersed repeats and other mementos of transposable elements in mammalian genomes
Smit, A. F. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00031-3 · Cited by 949 · see citing works
Endogenous viruses: insights into viral evolution and impact on host biology
Feschotte, C., & Gilbert, C. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3199 · Cited by 885 · see citing works
Immune Responses to Viral Gene Therapy Vectors
Shirley, J. L., de Jong, Y. P., Terhorst, C., & Herzog, R. W. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.01.001 · Cited by 788 · see citing works
Kojima, R., Bojar, D., Rizzi, G., Hamri, G. C.-E., El-Baba, M. D., Saxena, P., Ausländer, S., Tan, K. R., & Fussenegger, M. (2018) · Nature Communications · doi:10.1038/s41467-018-03733-8 · Cited by 748 · see citing works
A cell atlas of human thymic development defines T cell repertoire formation
Park, J.-E., Botting, R. A., Conde, C. D., Popescu, D.-M., Lavaert, M., Kunz, D. J., Goh, I., Stephenson, E., Ragazzini, R., Tuck, E. J., et al. (2020) · Science · doi:10.1126/science.aay3224 · Cited by 725 · see citing works
Pastuzyn, E. D., Day, C. E., Kearns, R. B., Kyrke‐Smith, M., Taibi, A. V., McCormick, J. F., Yoder, N., Belnap, D. M., Erlendsson, S., Morado, D. R., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.024 · Cited by 642 · see citing works
Retrotransposons Revisited: The Restraint and Rehabilitation of Parasites
Goodier, J. L., & Kazazian, H. H. (2008) · Cell · doi:10.1016/j.cell.2008.09.022 · Cited by 627 · see citing works
Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons
Ashley, J., Cordy, B., Lucia, D., Fradkin, L. G., Budnik, V., & Thomson, T. (2018) · Cell · doi:10.1016/j.cell.2017.12.022 · Cited by 488 · see citing works
Ono, R., Nakamura, K., Inoue, K., Naruse, M., Usami, T., Wakisaka‐Saito, N., Hino, T., Suzuki-Migishima, R., Ogonuki, N., Miki, H., et al. (2005) · Nature Genetics · doi:10.1038/ng1699 · Cited by 455 · see citing works
Arc in synaptic plasticity: from gene to behavior
Korb, E., & Finkbeiner, S. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.08.007 · Cited by 388 · see citing works
Dupressoír, A., Vernochet, C., Bawa, O., Harper, F., Pierron, G., Opolon, P., & Heidmann, T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902925106 · Cited by 364 · see citing works
Mangeot, P. E., Risson, V., Fusil, F., Marnef, A., Laurent, E., Blin, J., Mournetas, V., Massouridès, E., Sohier, T. J. M., Corbin, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-07845-z · Cited by 346 · see citing works
Multiple origins of viral capsid proteins from cellular ancestors
Krupovìč, M., & Koonin, E. V. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621061114 · Cited by 284 · see citing works
Self-citationA Retrotransposon-Derived Gene, PEG10, Is a Novel Imprinted Gene Located on Human Chromosome 7q21
Ono, R., Kobayashi, S., Wagatsuma, H., Aisaka, K., Kohda, T., Kaneko‐Ishino, T., & Ishino, F. (2001) · Genomics · doi:10.1006/geno.2001.6494 · Cited by 268 · see citing works
Moore, M. J., Zhang, C., Gantman, E. C., Mele, A., Darnell, J. C., & Darnell, R. B. (2014) · Nature Protocols · doi:10.1038/nprot.2014.012 · Cited by 251 · see citing works
A platform for actively loading cargo RNA to elucidate limiting steps in EV‐mediated delivery
Hung, M. E., & Leonard, J. N. (2016) · Journal of Extracellular Vesicles · doi:10.3402/jev.v5.31027 · Cited by 251 · see citing works
Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment
Ridder, K., Sevko, A., Heide, J., Dams, M., Rupp, A.-K., Macas, J., Starmann, J., Tjwa, M., Plate, K., Sültmann, H., et al. (2015) · Oncoimmunology · doi:10.1080/2162402x.2015.1008371 · Cited by 243 · see citing works
Protein delivery using engineered virus-like particles
Kaczmarczyk, S. J., Sitaraman, K., Young, H. A., Hughes, S. H., & Chatterjee, D. K. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101874108 · Cited by 220 · see citing works
Pastuzyn, E. D., Day, C. E., Kearns, R. B., Kyrke-Smith, M., Taibi, A. V., McCormick, J., Yoder, N., Belnap, D. M., Erlendsson, S., Morado, D. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.024 · Cited by 213 · see citing works
Käll, L., Storey, J. D., & Noble, W. S. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn294 · Cited by 203 · see citing works
CRIS.py: A Versatile and High-throughput Analysis Program for CRISPR-based Genome Editing
Connelly, J. P., & Pruett‐Miller, S. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-40896-w · Cited by 174 · see citing works
Wallace, C. S., Lyford, G. L., Worley, P. F., & Steward, O. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-01-00026.1998 · Cited by 171 · see citing works
Computational characterization of multiple Gag-like human proteins
Campillos, M., Doerks, T., Shah, P., & Peer Bork, B. (2006) · Trends in Genetics · doi:10.1016/j.tig.2006.09.006 · Cited by 168 · see citing works
Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1.
Okabe, H., Satoh, S., Furukawa, Y., Kato, T., Hasegawa, S., Nakajima, Y., Yamaoka, Y., & Nakamura, Y. (2003) · PubMed · Cited by 163 · see citing works
Paleovirology—ghosts and gifts of viruses past
Patel, M. R., Emerman, M., & Malik, H. S. (2011) · Current Opinion in Virology · doi:10.1016/j.coviro.2011.06.007 · Cited by 138 · see citing works
Shigemoto, K., Brennan, J., Walls, E., Watson, C. J., Stott, D., Rigby, P. W. J., & Reith, A. D. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.19.4079 · Cited by 109 · see citing works
Nostrand, E. L. V., Nguyen, T. B., Gelboin-Burkhart, C. A., Wang, R., Blue, S. M., Pratt, G. A., Louie, A. L., & Yeo, G. W.-M. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7204-3_14 · Cited by 107 · see citing works
The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification
Abed, M., Verschueren, E., Budayeva, H. G., Liu, P. J., Kirkpatrick, D. S., Reja, R., Kummerfeld, S., Webster, J. D., Gierke, S., Reichelt, M., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0214110 · Cited by 78 · see citing works
Emergence of vertebrate retroviruses and envelope capture
Kim, F. J., Battini, J., Manel, N., & Sitbon, M. (2003) · Virology · doi:10.1016/j.virol.2003.09.026 · Cited by 77 · see citing works
Arc is a flexible modular protein capable of reversible self-oligomerization
Myrum, C., Baumann, A., Bustad, H. J., Flydal, M. I., Mariaule, V., Alvira, S., Cuéllar, J., Haavik, J., Soule, J. D., Valpuesta, J., et al. (2015) · Biochemical Journal · doi:10.1042/bj20141446 · Cited by 69 · see citing works
Novel lentiviral vectors with mutated reverse transcriptase for mRNA delivery of TALE nucleases
Mock, U., Riecken, K., Berdien, B., Qasim, W., Chan, E., Cathomen, T., & Fehse, B. (2014) · Scientific Reports · doi:10.1038/srep06409 · Cited by 68 · see citing works
Structure of the Ty3/Gypsy retrotransposon capsid and the evolution of retroviruses
Dodonova, S., Prinz, S., Bilanchone, V., Sandmeyer, S. B., & Briggs, J. A. G. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900931116 · Cited by 55 · see citing works
Ty3/Gypsy Retrotransposon Fossils in Mammalian Genomes: Did They Evolve into New Cellular Functions?
Volff, J., Körting, C., & Schartl, M. (2001) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a003801 · Cited by 51 · see citing works
Henke, C., Strissel, P. L., Schubert, M.-T., Mitchell, M., Stolt, C. C., Faschingbauer, F., Beckmann, M. W., & Strick, R. (2015) · Retrovirology · doi:10.1186/s12977-015-0138-8 · Cited by 42 · see citing works
PEG10 is associated with treatment-induced neuroendocrine prostate cancer
Kim, S., Thaper, D., Bidnur, S., Toren, P., Akamatsu, S., Bishop, J. L., Collins, C. C., Vahid, S., & Zoubeidi, A. (2019) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0226 · Cited by 37 · see citing works
Functional Study of the Retrotransposon-Derived Human PEG10 Protease
Golda, M., Mótyán, J. A., Mahdi, M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072424 · Cited by 34 · see citing works
Guio, L., & González, J. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9074-0_16 · Cited by 31 · see citing works
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de la Peña, J. B., Barragán‐Iglesias, P., Lou, T., Kunder, N., Loerch, S., Shukla, T. N., Basavarajappa, L., Song, J. J., James, D., Megat, S., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0440-21.2021 · Cited by 28 · see citing works
Self-citationPaternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion, and Survival of Bladder Cancer
Kawai, Y., Imada, K., Akamatsu, S., Zhang, F., Seiler, R., Hayashi, T., Leong, J., Beraldi, E., Saxena, N., Kretschmer, A., et al. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-1031 · Cited by 27 · see citing works
Self-citationLiang, J., Liu, N., & Xin, H. (2019) · General Physiology and Biophysics · doi:10.4149/gpb_2019018 · Cited by 18 · see citing works
Challis, R. C., Kumar, S. R., Chan, K. Y., Challis, C., Jang, M. J., Rajendran, P. S., Tompkins, J. D., Shivkumar, K., Deverman, B. E., & Gradinaru, V. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/246405 · Cited by 17 · see citing works
Sequence requirements for localization and packaging of Ty3 retroelement RNA
Clemens, K., Bilanchone, V., Beliakova-Bethell, N., Larsen, L. S. Z., Nguyen, K. D., & Sandmeyer, S. (2012) · Virus Research · doi:10.1016/j.virusres.2012.10.008 · Cited by 8 · see citing works
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Barragán‐Iglesias, P., de la Peña, J. B., Lou, T., et al. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3684856 · Cited by 5 · see citing works
Coquin, Y., Ferrand, M., Seye, A. K., Menu, L., & Galy, A. H. M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/816223 · Cited by 2 · see citing works
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- Authors
- Segel, M., Lash, B., Song, J., Ladha, A., Liu, C. C., Jin, X., Mekhedov, S. L., Macrae, R. K., Koonin, E. V., & Zhang, F.
- Affiliations
- Broad Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Zhang, Feng
- ORCID
- Venue
- Science
- Published
- 2021-08-20
- Volume
- 373
- Issue
- 6557
- Pages
- 882-889
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8431961
- OpenAlex
- W3194369044
- Cited by
- 423
- References
- 58
- Citations by year
- 2026: 62 · 2025: 77 · 2024: 104 · 2023: 96 · 2022: 71 · 2021: 12 · 2012: 1
- FWCI
- 22.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health (1R01-HG009761, 1DP1-HL141201)
- Howard Hughes Medical Institute
- G Harold and Leila Y. Mathers Foundation
- Edward Mallinckrodt, Jr. Foundation
- Open Philanthropy Project
- Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT
- Poitras Center for Psychiatric Disorders Research at MIT
- Yang-Tan Center for Molecular Therapeutics at MIT
- Simons Center for the Social Brain at MIT
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- PEG10, retroelements, virus-like particles, mRNA delivery, pseudotyping, fusogens, extracellular secretion
- MeSH terms
- Extracellular Vesicles, Protein Domains, Gene Editing, Animals, Capsid, Cell Line, DNA-Binding Proteins, Genetic Vectors, Humans, Neurons, RNA, Messenger, Transfection, Up-Regulation, RNA-Binding Proteins, Retroelements, Untranslated Regions, Apoptosis Regulatory Proteins, Mice
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