Ancestral library identifies conserved reprogrammable liver motif on AAV capsid

Cell Reports Medicine - Tập 3 - Trang 100803 - 2022
Eric Zinn1,2,3,4, Carmen Unzu1,2,3,4, Pauline F. Schmit1,2,3,4, Heikki T. Turunen1,2,3,4, Nerea Zabaleta1,2,3,4, Julio Sanmiguel1,2,3,4, Allegra Fieldsend1,2,3,4, Urja Bhatt1,2,3,4, Cheikh Diop1,2,3,4, Erin Merkel1,2,3,4, Rakesh Gurrala1,2,3,4, Bryan Peacker4,5,6, Christopher Rios4,5,6, Kathleen Messemer4,5,6, Jennifer Santos1,2,3,4, Reynette Estelien1,2,3,4, Eva Andres-Mateos1,2,3,4, Amy J. Wagers4,5,6,7, Christopher Tipper1,2,3,4, Luk H. Vandenberghe1,2,3,4
1Grousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA, USA
2Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
3The Broad Institute of Harvard and MIT, Cambridge, MA, USA
4Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
5Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
6Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA
7Joslin Diabetes Center, Boston, MA 02215, USA

Tài liệu tham khảo

Li, 2020, Engineering adeno-associated virus vectors for gene therapy, Nat. Rev. Genet., 21, 255, 10.1038/s41576-019-0205-4 Keeler, 2019, Recombinant adeno-associated virus gene therapy in light of luxturna (and zolgensma and glybera): where are we, and how did we get here?, Annu. Rev. Virol., 6, 601, 10.1146/annurev-virology-092818-015530 Hudry, 2019, Therapeutic AAV gene transfer to the nervous system: a clinical reality, Neuron, 101, 839, 10.1016/j.neuron.2019.02.017 Mendell, 2021, Current clinical applications of in vivo gene therapy with AAVs, Mol. Ther., 29, 464, 10.1016/j.ymthe.2020.12.007 Manno, 2006, Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response, Nat. Med., 12, 342, 10.1038/nm1358 Nathwani, 2011, Adenovirus-associated virus vector-mediated gene transfer in hemophilia B, N. Engl. J. Med., 365, 2357, 10.1056/NEJMoa1108046 Day, 2021, Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial, Lancet Neurol., 20, 284, 10.1016/S1474-4422(21)00001-6 Philippidis, 2020, After third death, audentes' AT132 remains on clinical hold, Hum. Gene Ther., 31, 908, 10.1089/hum.2020.29133.bfs Pulicherla, 2011, Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer, Mol. Ther., 19, 1070, 10.1038/mt.2011.22 Wang, 2018, A rationally engineered capsid variant of AAV9 for systemic CNS-directed and peripheral tissue-detargeted gene delivery in neonates, Mol. Ther. Methods Clin. Dev., 9, 234, 10.1016/j.omtm.2018.03.004 Rotundo, 2013, Use of a lower dosage liver-detargeted AAV vector to prevent hamster muscular dystrophy, Hum. Gene Ther., 24, 424, 10.1089/hum.2012.121 Gao, 2005, New recombinant serotypes of AAV vectors, Curr. Gene Ther., 5, 285, 10.2174/1566523054065057 Grimm, 2006, Liver transduction with recombinant adeno-associated virus is primarily restricted by capsid serotype not vector genotype, J. Virol., 80, 426, 10.1128/JVI.80.1.426-439.2006 Nakai, 2005, Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in mice, J. Virol., 79, 214, 10.1128/JVI.79.1.214-224.2005 Vandenberghe, 2009, Naturally occurring singleton residues in AAV capsid impact vector performance and illustrate structural constraints, Gene Ther., 16, 1416, 10.1038/gt.2009.101 Wu, 2006, Single amino acid changes can influence titer, heparin binding, and tissue tropism in different adeno-associated virus serotypes, J. Virol., 80, 11393, 10.1128/JVI.01288-06 Vandenberghe, 2006, Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid, Nat. Med., 12, 967, 10.1038/nm1445 Zhong, 2008, Next generation of adeno-associated virus 2 vectors: point mutations in tyrosines lead to high-efficiency transduction at lower doses, Proc. Natl. Acad. Sci. USA, 105, 7827, 10.1073/pnas.0802866105 Xie, 2002, The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy, Proc. Natl. Acad. Sci. USA, 99, 10405, 10.1073/pnas.162250899 Nam, 2007, Structure of adeno-associated virus serotype 8, a gene therapy vector, J. Virol., 81, 12260, 10.1128/JVI.01304-07 Opie, 2003, Identification of amino acid residues in the capsid proteins of adeno-associated virus type 2 that contribute to heparan sulfate proteoglycan binding, J. Virol., 77, 6995, 10.1128/JVI.77.12.6995-7006.2003 Kern, 2003, Identification of a heparin-binding motif on adeno-associated virus type 2 capsids, J. Virol., 77, 11072, 10.1128/JVI.77.20.11072-11081.2003 Asokan, 2010, Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle, Nat. Biotechnol., 28, 79, 10.1038/nbt.1599 Shen, 2013, Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency, J. Biol. Chem., 288, 28814, 10.1074/jbc.M113.482380 Maurer, 2018, The assembly-activating protein promotes stability and interactions between AAV's viral proteins to nucleate capsid assembly, Cell Rep., 23, 1817, 10.1016/j.celrep.2018.04.026 Dudek, 2020, GPR108 is a highly conserved AAV entry factor, Mol. Ther., 28, 367, 10.1016/j.ymthe.2019.11.005 Grimm, 2008, In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated viruses, J. Virol., 82, 5887, 10.1128/JVI.00254-08 Dalkara, 2013, In vivo-directed evolution of a new adeno-associated virus for therapeutic outer retinal gene delivery from the vitreous, Sci. Transl. Med., 5, 189ra76, 10.1126/scitranslmed.3005708 Lisowski, 2014, Selection and evaluation of clinically relevant AAV variants in a xenograft liver model, Nature, 506, 382, 10.1038/nature12875 Deverman, 2016, Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain, Nat. Biotechnol., 34, 204, 10.1038/nbt.3440 Hordeaux, 2018, The neurotropic properties of AAV-PHP.B are limited to C57BL/6J mice, Mol. Ther., 26, 664, 10.1016/j.ymthe.2018.01.018 Hordeaux, 2019, The GPI-linked protein LY6A drives AAV-PHP.B transport across the blood-brain barrier, Mol. Ther., 27, 912, 10.1016/j.ymthe.2019.02.013 Huang, 2019, Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids, PLoS One, 14, 10.1371/journal.pone.0225206 Ramachandran, 2017, Evaluation of dose and safety of AAV7m8 and AAV8BP2 in the non-human primate retina, Hum. Gene Ther., 28, 154, 10.1089/hum.2016.111 Paulk, 2018, Bioengineered viral platform for intramuscular passive vaccine delivery to human skeletal muscle, Mol. Ther. Methods Clin. Dev., 10, 144, 10.1016/j.omtm.2018.06.001 Paulk, 2018, Bioengineered AAV capsids with combined high human liver transduction in vivo and unique humoral seroreactivity, Mol. Ther., 26, 289, 10.1016/j.ymthe.2017.09.021 Marsic, 2014, Vector design Tour de Force: integrating combinatorial and rational approaches to derive novel adeno-associated virus variants, Mol. Ther., 22, 1900, 10.1038/mt.2014.139 Havlik, 2020, Coevolution of adeno-associated virus capsid antigenicity and tropism through a structure-guided approach, J. Virol., 94, 10.1128/JVI.00976-20 Albright, 2018, Mapping the structural determinants required for AAVrh.10 transport across the blood-brain barrier, Mol. Ther., 26, 510, 10.1016/j.ymthe.2017.10.017 Zinn, 2015, In silico reconstruction of the viral evolutionary lineage yields a potent gene therapy vector, Cell Rep., 12, 1056, 10.1016/j.celrep.2015.07.019 Wong, 2016, Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM, Proc. Natl. Acad. Sci. USA, 113, 2544, 10.1073/pnas.1517883113 Wong, 2015, Massively parallel high-order combinatorial genetics in human cells, Nat. Biotechnol., 33, 952, 10.1038/nbt.3326 Adachi, 2014, Drawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing, Nat. Commun., 5, 3075, 10.1038/ncomms4075 Ogden, 2019, Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design, Science, 366, 1139, 10.1126/science.aaw2900 Weinmann, 2020, Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants, Nat. Commun., 11, 5432, 10.1038/s41467-020-19230-w Brown, 2021, Deep parallel characterization of AAV tropism and AAV-mediated transcriptional changes via single-cell RNA sequencing, Front. Immunol., 12, 730825, 10.3389/fimmu.2021.730825 Davidsson, 2019, A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism, Proc. Natl. Acad. Sci. USA, 116, 27053, 10.1073/pnas.1910061116 Goertsen, 2022, AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset, Nat. Neurosci., 25, 106, 10.1038/s41593-021-00969-4 Öztürk, 2021, scAAVengr, a transcriptome-based pipeline for quantitative ranking of engineered AAVs with single-cell resolution, Elife, 10, 10.7554/eLife.64175 Ellis, 2013, A survey of ex vivo/in vitro transduction efficiency of mammalian primary cells and cell lines with Nine natural adeno-associated virus (AAV1-9) and one engineered adeno-associated virus serotype, Virol. J., 10, 74, 10.1186/1743-422X-10-74 Thomas, 2004, Rapid uncoating of vector genomes is the key to efficient liver transduction with pseudotyped adeno-associated virus vectors, J. Virol., 78, 3110, 10.1128/JVI.78.6.3110-3122.2004 Wang, 2015, Comparative study of liver gene transfer with AAV vectors based on natural and engineered AAV capsids, Mol. Ther., 23, 1877, 10.1038/mt.2015.179 Landegger, 2017, A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear, Nat. Biotechnol., 35, 280, 10.1038/nbt.3781 Ikeda, 2018, Efficient gene transfer to kidney mesenchymal cells using a synthetic adeno-associated viral vector, J. Am. Soc. Nephrol., 29, 2287, 10.1681/ASN.2018040426 Carvalho, 2018, Synthetic adeno-associated viral vector efficiently targets mouse and nonhuman primate retina in vivo, Hum. Gene Ther., 29, 771, 10.1089/hum.2017.154 Hudry, 2018, Efficient gene transfer to the central nervous system by single-stranded Anc80L65, Mol. Ther. Methods Clin. Dev., 10, 197, 10.1016/j.omtm.2018.07.006 Wu, 2000, Mutational analysis of the adeno-associated virus type 2 (AAV2) capsid gene and construction of AAV2 vectors with altered tropism, J. Virol., 74, 8635, 10.1128/JVI.74.18.8635-8647.2000 Lochrie, 2006, Mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization, J. Virol., 80, 821, 10.1128/JVI.80.2.821-834.2006 Guo, 2004, Protein tolerance to random amino acid change, Proc. Natl. Acad. Sci. USA, 101, 9205, 10.1073/pnas.0403255101 Schmit, 2020, Cross-packaging and capsid mosaic formation in multiplexed AAV libraries, Mol. Ther. Methods Clin. Dev., 17, 107, 10.1016/j.omtm.2019.11.014 Cabanes-Creus, 2021, Single amino acid insertion allows functional transduction of murine hepatocytes with human liver tropic AAV capsids, Mol. Ther. Methods Clin. Dev., 21, 607, 10.1016/j.omtm.2021.04.010 Lerch, 2010, The structure of adeno-associated virus serotype 3B (AAV-3B): insights into receptor binding and immune evasion, Virology, 403, 26, 10.1016/j.virol.2010.03.027 Govindasamy, 2006, Structurally mapping the diverse phenotype of adeno-associated virus serotype 4, J. Virol., 80, 11556, 10.1128/JVI.01536-06 Govindasamy, 2013, Structural insights into adeno-associated virus serotype 5, J. Virol., 87, 11187, 10.1128/JVI.00867-13 Xie, 2011, Structure–function analysis of receptor-binding in adeno-associated virus serotype 6 (AAV-6), Virology, 420, 10, 10.1016/j.virol.2011.08.011 DiMattia, 2012, Structural insight into the unique properties of adeno-associated virus serotype 9, J. Virol., 86, 6947, 10.1128/JVI.07232-11 Mikals, 2014, The structure of AAVrh32.33, a novel gene delivery vector, J. Struct. Biol., 186, 308, 10.1016/j.jsb.2014.03.020 Halder, 2015, Structure of neurotropic adeno-associated virus AAVrh.8, J. Struct. Biol., 192, 21, 10.1016/j.jsb.2015.08.017 Bryant, 2021, Deep diversification of an AAV capsid protein by machine learning, Nat. Biotechnol., 39, 691, 10.1038/s41587-020-00793-4 Pekrun, 2019, Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors, JCI Insight, 4, 131610, 10.1172/jci.insight.131610 Li, 2015, Efficient and targeted transduction of nonhuman primate liver with systemically delivered optimized AAV3B vectors, Mol. Ther., 23, 1867, 10.1038/mt.2015.174 Bevan, 2011, Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders, Mol. Ther., 19, 1971, 10.1038/mt.2011.157 Foust, 2010, Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN, Nat. Biotechnol., 28, 271, 10.1038/nbt.1610 Kornegay, 2010, Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs, Mol. Ther., 18, 1501, 10.1038/mt.2010.94 Hinderer, 2018, Severe toxicity in nonhuman primates and piglets following high-dose intravenous administration of an adeno-associated virus vector expressing human SMN, Hum. Gene Ther., 29, 285, 10.1089/hum.2018.015 Meyer, 2019, Structure of the gene therapy vector, adeno-associated virus with its cell receptor, Elife, 8, 10.7554/eLife.44707 Zhang, 2019, Adeno-associated virus 2 bound to its cellular receptor AAVR, Nat. Microbiol., 4, 675, 10.1038/s41564-018-0356-7 Dudek, 2018, An alternate route for adeno-associated virus (AAV) entry independent of AAV receptor, J. Virol., 92, 10.1128/JVI.02213-17 Pillay, 2016, An essential receptor for adeno-associated virus infection, Nature, 530, 108, 10.1038/nature16465 Kasai, 2018, HuH-7 reference genome profile: complex karyotype composed of massive loss of heterozygosity, Hum. Cell, 31, 261, 10.1007/s13577-018-0212-3 Wang, 2010, The pleiotropic effects of natural AAV infections on liver-directed gene transfer in macaques, Mol. Ther., 18, 126, 10.1038/mt.2009.245 Lock, 2010, Rapid, simple, and versatile manufacturing of recombinant adeno-associated viral vectors at scale, Hum. Gene Ther., 21, 1259, 10.1089/hum.2010.055 Sanmiguel, 2019, Quantitative and digital droplet-based AAV genome titration, Methods Mol. Biol., 1950, 51, 10.1007/978-1-4939-9139-6_4