Identification of adeno-associated virus variants for gene transfer into human neural cell types by parallel capsid screening.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 05 2022
19 05 2022
Historique:
received:
31
08
2021
accepted:
09
05
2022
entrez:
19
5
2022
pubmed:
20
5
2022
medline:
24
5
2022
Statut:
epublish
Résumé
Human brain cells generated by in vitro cell programming provide exciting prospects for disease modeling, drug discovery and cell therapy. These applications frequently require efficient and clinically compliant tools for genetic modification of the cells. Recombinant adeno-associated viruses (AAVs) fulfill these prerequisites for a number of reasons, including the availability of a myriad of AAV capsid variants with distinct cell type specificity (also called tropism). Here, we harnessed a customizable parallel screening approach to assess a panel of natural or synthetic AAV capsid variants for their efficacy in lineage-related human neural cell types. We identified common lead candidates suited for the transduction of directly converted, early-stage induced neural stem cells (iNSCs), induced pluripotent stem cell (iPSC)-derived later-stage, radial glia-like neural progenitors, as well as differentiated astrocytic and mixed neuroglial cultures. We then selected a subset of these candidates for functional validation in iNSCs and iPSC-derived astrocytes, using shRNA-induced downregulation of the citrate transporter SLC25A1 and overexpression of the transcription factor NGN2 for proofs-of-concept. Our study provides a comparative overview of the susceptibility of different human cell programming-derived brain cell types to AAV transduction and a critical discussion of the assets and limitations of this specific AAV capsid screening approach.
Identifiants
pubmed: 35589936
doi: 10.1038/s41598-022-12404-0
pii: 10.1038/s41598-022-12404-0
pmc: PMC9120183
doi:
Substances chimiques
Capsid Proteins
0
Mitochondrial Proteins
0
Organic Anion Transporters
0
Slc25a1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
8356Subventions
Organisme : NIH HHS
ID : R01 NS100514
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).
pubmed: 16904174
doi: 10.1016/j.cell.2006.07.024
Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
pubmed: 18035408
doi: 10.1016/j.cell.2007.11.019
Flitsch, L. J., Laupman, K. E. & Brüstle, O. Transcription factor-based fate specification and forward programming for neural regeneration. Front. Cell. Neurosci. 14, 1–22 (2020).
doi: 10.3389/fncel.2020.00121
Flitsch, L. J. & Brüstle, O. Evolving principles underlying neural lineage conversion and their relevance for biomedical translation. F1000Research 8, 1548 (2019).
doi: 10.12688/f1000research.18926.1
Mertens, J., Marchetto, M. C., Bardy, C. & Gage, F. H. Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience. Nat. Rev. Neurosci. 17, 424–437 (2016).
pubmed: 27194476
pmcid: 6276815
doi: 10.1038/nrn.2016.46
Barker, R. A., Götz, M. & Parmar, M. New approaches for brain repair—from rescue to reprogramming. Nature 557, 329–334 (2018).
pubmed: 29769670
doi: 10.1038/s41586-018-0087-1
Mattugini, N. et al. Inducing different neuronal subtypes from astrocytes in the injured mouse cerebral cortex. Neuron 103, 1086-1095.e5 (2019).
pubmed: 31488328
pmcid: 6859713
doi: 10.1016/j.neuron.2019.08.009
Rivetti Di Val Cervo, P. et al. Induction of functional dopamine neurons from human astrocytes in vitro and mouse astrocytes in a Parkinson’s disease model. Nat. Biotechnol. 35, 444–452 (2017).
pubmed: 28398344
doi: 10.1038/nbt.3835
Rezvani, M. et al. In vivo hepatic reprogramming of myofibroblasts with AAV vectors as a therapeutic strategy for liver fibrosis. Cell Stem Cell 18, 809–816 (2016).
pubmed: 27257763
pmcid: 5325707
doi: 10.1016/j.stem.2016.05.005
Senís, E. et al. AAV vector-mediated in vivo reprogramming into pluripotency. Nat. Commun. 9, 1–14 (2018).
doi: 10.1038/s41467-018-05059-x
Kotterman, M. A. & Schaffer, D. V. Engineering adeno-associated viruses for clinical gene therapy. Nat. Rev. Genet. 15, 445–451 (2014).
pubmed: 24840552
pmcid: 4393649
doi: 10.1038/nrg3742
Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358–378 (2019).
pubmed: 30710128
pmcid: 6927556
doi: 10.1038/s41573-019-0012-9
Hammond, S. L., Leek, A. N., Richman, E. H. & Tjalkens, R. B. Cellular selectivity of AAV serotypes for gene delivery in neurons and astrocytes by neonatal intracerebroventricular injection. PLoS ONE 12, 1–22 (2017).
doi: 10.1371/journal.pone.0188830
Kunze, C. et al. Synthetic AAV/CRISPR vectors for blocking HIV-1 expression in persistently infected astrocytes. Glia 66, 413–427 (2018).
pubmed: 29119608
doi: 10.1002/glia.23254
Duong, T. T. et al. Comparative AAV-EGFP transgene expression using vector serotypes 1–9, 7M8, and 8b in human pluripotent stem cells, RPEs, and human and rat cortical neurons. Stem Cells Int. 2019, 7281912 (2019).
pubmed: 30800164
pmcid: 6360060
doi: 10.1155/2019/7281912
Rapti, K. et al. Effectiveness of gene delivery systems for pluripotent and differentiated cells. Mol. Ther. Methods Clin. Dev. 2, 14067 (2015).
pubmed: 26052535
pmcid: 4449028
doi: 10.1038/mtm.2014.67
Hudry, E. & Vandenberghe, L. H. Therapeutic AAV gene transfer to the nervous system: A clinical reality. Neuron 101, 839–862 (2019).
pubmed: 30844402
doi: 10.1016/j.neuron.2019.02.017
Li, C. & Samulski, R. J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 21, 255–272 (2020).
pubmed: 32042148
doi: 10.1038/s41576-019-0205-4
Börner, K. et al. Pre-arrayed pan-AAV peptide display libraries for rapid single-round screening. Mol. Ther. 28, 1016–1032 (2020).
pubmed: 32105604
pmcid: 7132618
doi: 10.1016/j.ymthe.2020.02.009
Sheng, C. et al. A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation. Nat. Commun. 9, 4047 (2018).
pubmed: 30279449
pmcid: 6168501
doi: 10.1038/s41467-018-06398-5
Reinhardt, P. et al. Derivation and expansion using only small molecules of human neural progenitors for neurodegenerative disease modeling. PLoS ONE 8, e59252 (2013).
pubmed: 23533608
pmcid: 3606479
doi: 10.1371/journal.pone.0059252
Koch, P., Opitz, T., Steinbeck, J. A., Ladewig, J. & Brustle, O. A rosette-type, self-renewing human ES cell-derived neural stem cell with potential for in vitro instruction and synaptic integration. Proc. Natl. Acad. Sci. 106, 3225–3230 (2009).
pubmed: 19218428
pmcid: 2651316
doi: 10.1073/pnas.0808387106
Gorris, R. et al. Pluripotent stem cell-derived radial glia-like cells as stable intermediate for efficient generation of human oligodendrocytes. Glia 63, 2152–2167 (2015).
pubmed: 26123132
doi: 10.1002/glia.22882
Peitz, M., Krutenko, T. & Brüstle, O. Protocol for the standardized generation of forward programmed cryopreservable excitatory and inhibitory forebrain neurons. STAR Protoc. 1, 100038 (2020).
pubmed: 33111086
pmcid: 7580116
doi: 10.1016/j.xpro.2020.100038
Cearley, C. N. et al. Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain. Mol. Ther. 16, 1710–1718 (2008).
pubmed: 18714307
doi: 10.1038/mt.2008.166
Shi, W. & Bartlett, J. S. RGD inclusion in VP3 provides adeno-associated virus type 2 (AAV2)-based vectors with a heparan sulfate-independent cell entry mechanism. Mol. Ther. 7, 515–525 (2003).
pubmed: 12727115
doi: 10.1016/S1525-0016(03)00042-X
Stachler, M. D. & Bartlett, J. S. Mosaic vectors comprised of modified AAV1 capsid proteins for efficient vector purification and targeting to vascular endothelial cells. Gene Ther. 13, 926–931 (2006).
pubmed: 16482202
doi: 10.1038/sj.gt.3302738
Sayroo, R. et al. Development of novel AAV serotype 6 based vectors with selective tropism for human cancer cells. Gene Ther. 23, 18–25 (2016).
pubmed: 26270885
doi: 10.1038/gt.2015.89
Kunji, E. R. S., King, M. S., Ruprecht, J. J. & Thangaratnarajah, C. The SLC25 carrier family: Important transport proteins in mitochondrial physiology and pathology. Physiology 35, 302–327 (2020).
pubmed: 32783608
doi: 10.1152/physiol.00009.2020
Palmieri, F. Mitochondrial transporters of the SLC25 family and associated diseases: A review. J. Inherit. Metab. Dis. 37, 565–575 (2014).
pubmed: 24797559
doi: 10.1007/s10545-014-9708-5
Zhang, Y. et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78, 785–798 (2013).
pubmed: 23764284
pmcid: 3751803
doi: 10.1016/j.neuron.2013.05.029
Grande, A. et al. Environmental impact on direct neuronal reprogramming in vivo in the adult brain. Nat. Commun. 4, 2373 (2013).
pubmed: 23974433
doi: 10.1038/ncomms3373
Götz, M., Stoykova, A. & Gruss, P. Pax6 controls radial glia differentiation in the cerebral cortex. Neuron 21, 1031–1044 (1998).
pubmed: 9856459
doi: 10.1016/S0896-6273(00)80621-2
Heins, N. et al. Glial cells generate neurons: The role of the transcription factor Pax6. Nat. Neurosci. 5, 308–315 (2002).
pubmed: 11896398
doi: 10.1038/nn828
Hack, M. A., Sugimori, M., Lundberg, C., Nakafuku, M. & Götz, M. Regionalization and fate specification in neurospheres: The role of Olig2 and Pax6. Mol. Cell. Neurosci. 25, 664–678 (2004).
pubmed: 15080895
doi: 10.1016/j.mcn.2003.12.012
Kallur, T., Gisler, R., Lindvall, O. & Kokaia, Z. Pax6 promotes neurogenesis in human neural stem cells. Mol. Cell. Neurosci. 38, 616–628 (2008).
pubmed: 18595732
doi: 10.1016/j.mcn.2008.05.010
Osumi, N., Shinohara, H., Numayama-Tsuruta, K. & Maekawa, M. Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem Cells 26, 1663–1672 (2008).
pubmed: 18467663
doi: 10.1634/stemcells.2007-0884
Sansom, S. N. et al. The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis. PLoS Genet. 5, 20–23 (2009).
doi: 10.1371/journal.pgen.1000511
Kronenberg, G. et al. Modulation of fate determinants Olig2 and Pax6 in resident glia evokes spiking neuroblasts in a model of mild brain ischemia. Stroke 41, 2944–2949 (2010).
pubmed: 21051674
doi: 10.1161/STROKEAHA.110.583039
Thakurela, S. et al. Mapping gene regulatory circuitry of Pax6 during neurogenesis. Cell Discov. 2, 15045 (2016).
pubmed: 27462442
pmcid: 4860964
doi: 10.1038/celldisc.2015.45
Excoffon, K. J. D. A. et al. Directed evolution of adeno-associated virus to an infectious respiratory virus. Proc. Natl. Acad. Sci. U. S. A. 106, 3865–3870 (2009).
pubmed: 19237554
pmcid: 2646629
doi: 10.1073/pnas.0813365106
Asuri, P. et al. Directed evolution of adeno-associated virus for enhanced gene delivery and gene targeting in human pluripotent stem cells. Mol. Ther. 20, 329–338 (2012).
pubmed: 22108859
doi: 10.1038/mt.2011.255
Jang, J. H. et al. An evolved adeno-associated viral variant enhances gene delivery and gene targeting in neural stem cells. Mol. Ther. 19, 667–675 (2011).
pubmed: 21224831
pmcid: 3070092
doi: 10.1038/mt.2010.287
Ravindra Kumar, S. et al. Multiplexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types. Nat. Methods 17, 541–550 (2020).
pubmed: 32313222
doi: 10.1038/s41592-020-0799-7
Naumer, M., Popa-Wagner, R. & Kleinschmidt, J. A. Impact of capsid modifications by selected peptide ligands on recombinant adeno-associated virus serotype 2-mediated gene transduction. J. Gen. Virol. 93, 2131–2141 (2012).
pubmed: 22764318
doi: 10.1099/vir.0.044735-0
Grimm, D. et al. In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of Adeno-associated viruses. J. Virol. 82, 5887–5911 (2008).
pubmed: 18400866
pmcid: 2395137
doi: 10.1128/JVI.00254-08
Körbelin, J. et al. Optimization of design and production strategies for novel adeno-associated viral display peptide libraries. Gene Ther. 24, 470–481 (2017).
pubmed: 28622288
doi: 10.1038/gt.2017.51
Müller, O. J. et al. Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. Nat. Biotechnol. 21, 1040–1046 (2003).
pubmed: 12897791
doi: 10.1038/nbt856
Perabo, L. et al. In vitro selection of viral vectors with modified tropism: The adeno-associated virus display. Mol. Ther. 8, 151–157 (2003).
pubmed: 12842438
doi: 10.1016/S1525-0016(03)00123-0
Waterkamp, D. A., Müller, O. J., Ying, Y., Trepel, M. & Kleinschmidt, J. A. Isolation of targeted AAV2 vectors from novel virus display libraries. J. Gene Med. 8, 1307–1319 (2006).
pubmed: 16955542
doi: 10.1002/jgm.967
Tabebordbar, M. et al. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell 184, 4919-4938.e22 (2021).
pubmed: 34506722
doi: 10.1016/j.cell.2021.08.028
Weinmann, J. et al. Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants. Nat. Commun. 11, 5432 (2020).
pubmed: 33116134
pmcid: 7595228
doi: 10.1038/s41467-020-19230-w
Bönnemann, C. G. Designer AAV muscle up. Cell 184, 4845–4847 (2021).
pubmed: 34534462
doi: 10.1016/j.cell.2021.08.031
Zolotukhin, S., Trivedi, P. D., Corti, M. & Byrne, B. J. Scratching the surface of RGD-directed AAV capsid engineering. Mol. Ther. 29, 3099–3100 (2021).
pubmed: 34699781
doi: 10.1016/j.ymthe.2021.10.020
Latour, Y. L. et al. Human GLB1 knockout cerebral organoids: A model system for testing AAV9-mediated GLB1 gene therapy for reducing GM1 ganglioside storage in GM1 gangliosidosis. Mol. Genet. Metab. Reports 21, 100513 (2019).
doi: 10.1016/j.ymgmr.2019.100513
Chen, Y. C. et al. A NeuroD1 AAV-based gene therapy for functional brain repair after ischemic injury through in vivo astrocyte-to-neuron conversion. Mol. Ther. 28, 1–18 (2019).
Wu, Z. et al. Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington’s disease. Nat. Commun. 11, 1–18 (2020).
Kremer, L. P. et al. High throughput screening of novel AAV capsids identifies variants for transduction of adult NSCs within the subventricular zone. Mol. Ther. Methods Clin. Dev. 23, 33–50 (2021).
pubmed: 34553001
pmcid: 8427210
doi: 10.1016/j.omtm.2021.07.001
Powell, S. K., Samulski, R. J. & McCown, T. J. AAV capsid-promoter interactions determine CNS cell-selective gene expression in vivo. Mol. Ther. 28, 1373–1380 (2020).
pubmed: 32213322
pmcid: 7210720
doi: 10.1016/j.ymthe.2020.03.007
Grimm, D. Production methods for gene transfer vectors based on adeno-associated virus serotypes. Methods 28, 146–157 (2002).
pubmed: 12413413
doi: 10.1016/S1046-2023(02)00219-0
Reichart, F. et al. Selective targeting of integrin αvβ8 by a highly active cyclic peptide. J. Med. Chem. 62, 2024–2037 (2019).
pubmed: 30657681
doi: 10.1021/acs.jmedchem.8b01588
Kapp, T. G. et al. A comprehensive evaluation of the activity and selectivity profile of ligands for RGD-binding integrins. Sci. Rep. 7, 39805 (2017).
pubmed: 28074920
pmcid: 5225454
doi: 10.1038/srep39805
Amoasii, L. et al. Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy. Sci. Transl. Med. 9, eaan8081 (2017).
pubmed: 29187645
pmcid: 5749406
doi: 10.1126/scitranslmed.aan8081
Börner, K. et al. From experimental setup to bioinformatics: An RNAi screening platform to identify host factors involved in HIV-1 replication. Biotechnol. J. 5, 39–49 (2010).
pubmed: 20013946
doi: 10.1002/biot.200900226
Kamentsky, L. et al. Improved structure, function and compatibility for Cell Profiler: Modular high-throughput image analysis software. Bioinformatics 27, 1179–1180 (2011).
pubmed: 21349861
pmcid: 3072555
doi: 10.1093/bioinformatics/btr095