Modulating Mitochondrial DNA Heteroplasmy with Mitochondrially Targeted Endonucleases.
Gene therapy
Genetic engineering
Oxidative phosphorylation
Restriction endonuclease
Zinc finger nuclease
mitoTALEN
Journal
Annals of biomedical engineering
ISSN: 1573-9686
Titre abrégé: Ann Biomed Eng
Pays: United States
ID NLM: 0361512
Informations de publication
Date de publication:
24 Aug 2022
24 Aug 2022
Historique:
received:
05
05
2022
accepted:
09
08
2022
entrez:
24
8
2022
pubmed:
25
8
2022
medline:
25
8
2022
Statut:
aheadofprint
Résumé
Mitochondria, mainly known as energy factories of eukaryotic cells, also exert several additional signaling and metabolic functions and are today recognized as major cellular biosynthetic and signaling hubs. Mitochondria possess their own genome (mitochondrial DNA-mtDNA), that encodes proteins essential for oxidative phosphorylation, and mutations in it are an important contributor to human disease. The mtDNA mutations often exist in heteroplasmic conditions, with both healthy and mutant versions of the mtDNA residing in patients' cells and the level of mutant mtDNA may vary between different tissues and organs and affect the clinical outcome of the disease. Thus, shifting the ratio between healthy and mutant mtDNA in patients' cells provides an intriguing therapeutic option for mtDNA diseases. In this review we describe current strategies for modulating mitochondrial heteroplasmy levels with engineered endonucleases including mitochondrially targeted TALENs and Zinc finger nucleases (ZFNs) and discuss their therapeutic potential. These gene therapy tools could in the future provide therapeutic help both for patients with mitochondrial disease as well as in preventing the transfer of pathogenic mtDNA mutations from a mother to her offspring.
Identifiants
pubmed: 36001180
doi: 10.1007/s10439-022-03051-7
pii: 10.1007/s10439-022-03051-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022. The Author(s).
Références
Ashley, M. V., P. J. Laipis, and W. W. Hauswirth. Rapid segregation of heteroplasmic bovine mitochondria. Nucleic Acids Res. 17:7325, 1989.
pubmed: 2798094
pmcid: 334812
doi: 10.1093/nar/17.18.7325
Bacman, S. R., J. H. K. Kauppila, C. V. Pereira, N. Nissanka, M. Miranda, M. Pinto, S. L. Williams, N. G. Larsson, J. B. Stewart, and C. T. Moraes. MitoTALEN reduces mutant mtDNA load and restores tRNAAla levels in a mouse model of heteroplasmic mtDNA mutation. Nat. Med. 24(11):1696–1700, 2018.
pubmed: 30250143
pmcid: 6942693
doi: 10.1038/s41591-018-0166-8
Bacman, S. R., S. L. Williams, D. Duan, and C. T. Moraes. Manipulation of mtDNA heteroplasmy in all striated muscles of newborn mice by AAV9-mediated delivery of a mitochondria-targeted restriction endonuclease. Gene Ther. 19:1101–1106, 2012.
pubmed: 22130448
doi: 10.1038/gt.2011.196
Bacman, S. R., S. L. Williams, S. Garcia, and C. T. Moraes. Organ-specific shifts in mtDNA heteroplasmy following systemic delivery of a mitochondria-targeted restriction endonuclease. Gene Ther. 17:713–720, 2010.
pubmed: 20220783
pmcid: 3175591
doi: 10.1038/gt.2010.25
Bacman, S. R., S. L. Williams, M. Pinto, S. Peralta, and C. T. Moraes. Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Nat. Med. 19(9):1111–1113, 2013.
pubmed: 23913125
pmcid: 4153471
doi: 10.1038/nm.3261
Boch, J., H. Scholze, S. Schornack, A. Landgraf, S. Hahn, S. Kay, T. Lahaye, A. Nickstadt, and U. Bonas. Breaking the code of DNA binding specificity of TAL-type III effectors. Science. 326:1509–1512, 2009.
pubmed: 19933107
doi: 10.1126/science.1178811
B1H screens of C2H2-ZF domainsat. http://zf.princeton.edu/b1h/index.html
Cao, L., H. Shitara, T. Horii, Y. Nagao, H. Imai, K. Abe, T. Hara, J. I. Hayashi, and H. Yonekawa. The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nat. Genet. 39:386–390, 2007.
pubmed: 17293866
doi: 10.1038/ng1970
Chan, D. C. Mitochondria: dynamic organelles in disease, aging, and development. Cell. 2006. https://doi.org/10.1016/j.cell.2006.06.010 .
doi: 10.1016/j.cell.2006.06.010
pubmed: 17174891
Chandel, N. S. Mitochondria as signaling organelles. BMC Biol. 12:1–7, 2014.
doi: 10.1186/1741-7007-12-1
Cree, L. M., D. C. Samuels, S. C. De Sousa Lopes, H. K. Rajasimha, P. Wonnapinij, J. R. Mann, H. H. M. Dahl, and P. F. Chinnery. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat. Genet. 40:249–254, 2008.
pubmed: 18223651
doi: 10.1038/ng.2007.63
Deng, D., C. Yan, X. Pan, M. Mahfouz, J. Wang, J. K. Zhu, Y. Shi, and N. Yan. Structural basis for sequence-specific recognition of DNA by TAL effectors. Science. 335:720–723, 2012.
pubmed: 22223738
pmcid: 3586824
doi: 10.1126/science.1215670
DiMauro, S., and G. Davidzon. Mitochondrial DNA and disease. Ann. Med. 2005. https://doi.org/10.1080/07853890510007368 .
doi: 10.1080/07853890510007368
pubmed: 16019721
DiMauro, S., and E. A. Schon. Mitochondrial respiratory-chain diseases. N. Engl. J. Med. 348:2656–2668, 2003.
pubmed: 12826641
doi: 10.1056/NEJMra022567
Doyle, E. L., N. J. Booher, D. S. Standage, D. F. Voytas, V. P. Brendel, J. K. Vandyk, and A. J. Bogdanove. TAL Effector-Nucleotide Targeter (TALE-NT) 2.0: tools for TAL effector design and target prediction. Nucleic Acids Res. 40:W117–W122, 2012.
pubmed: 22693217
pmcid: 3394250
doi: 10.1093/nar/gks608
Druzhyna, N. M., G. L. Wilson, and S. P. LeDoux. Mitochondrial DNA repair in aging and disease. Mech. Ageing Dev. 129:383–390, 2008.
pubmed: 18417187
pmcid: 2666190
doi: 10.1016/j.mad.2008.03.002
Freyer, C., L. M. Cree, A. Mourier, J. B. Stewart, C. Koolmeister, D. Milenkovic, T. Wai, V. I. Floros, E. Hagström, E. E. Chatzidaki, R. J. Wiesner, D. C. Samuels, N. G. Larsson, and P. F. Chinnery. Variation in germ line mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission. Nat. Genet. 44:1282, 2012.
pubmed: 23042113
pmcid: 3492742
doi: 10.1038/ng.2427
Gaj, T., C. A. Gersbach, and C. F. Barbas. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 31:397–405, 2013.
pubmed: 23664777
pmcid: 3694601
doi: 10.1016/j.tibtech.2013.04.004
Gammage, P. A., E. Gaude, L. Van Haute, P. Rebelo-Guiomar, C. B. Jackson, J. Rorbach, M. L. Pekalski, A. J. Robinson, M. Charpentier, J. P. Concordet, C. Frezza, and M. Minczuk. Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs. Nucleic Acids Res. 44:7804–7816, 2016.
pubmed: 27466392
pmcid: 5027515
doi: 10.1093/nar/gkw676
Gammage, P. A., C. T. Moraes, and M. Minczuk. Mitochondrial genome engineering: the revolution may not be CRISPR-Ized. Trends Genet. 34:101, 2018.
pubmed: 29179920
pmcid: 5783712
doi: 10.1016/j.tig.2017.11.001
Gammage, P. A., J. Rorbach, A. I. Vincent, E. J. Rebar, and M. Minczuk. Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations. EMBO Mol. Med. 6:458, 2014.
pubmed: 24567072
pmcid: 3992073
doi: 10.1002/emmm.201303672
Gammage, P. A., C. Viscomi, M. L. Simard, A. S. H. Costa, E. Gaude, C. A. Powell, L. Van Haute, B. J. McCann, P. Rebelo-Guiomar, R. Cerutti, L. Zhang, E. J. Rebar, M. Zeviani, C. Frezza, J. B. Stewart, and M. Minczuk. Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo. Nat. Med. 24:1691–1695, 2018.
pubmed: 30250142
pmcid: 6225988
doi: 10.1038/s41591-018-0165-9
Giles, R. E., H. Blanc, H. M. Cann, and D. C. Wallace. Maternal inheritance of human mitochondrial DNA. Proc. Natl. Acad. Sci. USA. 77:6715–6719, 1980.
pubmed: 6256757
pmcid: 350359
doi: 10.1073/pnas.77.11.6715
Gorman, G. S., P. F. Chinnery, S. DiMauro, M. Hirano, Y. Koga, R. McFarland, A. Suomalainen, D. R. Thorburn, M. Zeviani, and D. M. Turnbull. Mitochondrial diseases. Nat. Rev. Dis. Prim. 2(1):1–22, 2016.
Gray, M. W. Mitochondrial evolution. Cold Spring Harb. Perspect. Biol. 4:a011403, 2012.
pubmed: 22952398
pmcid: 3428767
doi: 10.1101/cshperspect.a011403
Guo, J., X. Chen, Z. Liu, H. Sun, Y. Zhou, Y. Dai, Y. Ma, L. He, X. Qian, J. Wang, J. Zhang, Y. Zhu, J. Zhang, B. Shen, and F. Zhou. DdCBE mediates efficient and inheritable modifications in mouse mitochondrial genome. Mol. Ther. - Nucleic Acids. 27:73–80, 2022.
pubmed: 34938607
doi: 10.1016/j.omtn.2021.11.016
Hamilton, G. The mitochondria mystery. Nature. 525:444–446, 2015.
pubmed: 26399812
doi: 10.1038/525444a
Hashimoto, M., S. R. Bacman, S. Peralta, M. J. Falk, A. Chomyn, D. C. Chan, S. L. Williams, and C. T. Moraes. MitoTALEN: a general approach to reduce mutant mtDNA loads and restore oxidative phosphorylation function in mitochondrial diseases. Mol. Ther. 23:1592–1599, 2015.
pubmed: 26159306
pmcid: 4817924
doi: 10.1038/mt.2015.126
Herrmann, J. M., and W. Neupert. Protein transport into mitochondria. Curr. Opin. Microbiol. 3:210–214, 2000.
pubmed: 10744987
doi: 10.1016/S1369-5274(00)00077-1
Holt, I. J., A. E. Harding, and J. A. Morgan-Hughes. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature. 331(6158):717–719, 1988.
pubmed: 2830540
doi: 10.1038/331717a0
Hoy, M. A. Molecular systematics and the evolution of arthropods. Insect Mol. Genet. 2013. https://doi.org/10.1016/B978-0-12-415874-0.00012-3 .
doi: 10.1016/B978-0-12-415874-0.00012-3
Jackson, C. B., D. M. Turnbull, M. Minczuk, and P. A. Gammage. Therapeutic manipulation of mtDNA Heteroplasmy: A Shifting Perspective. Trends Mol. Med. 26:698–709, 2020.
pubmed: 32589937
doi: 10.1016/j.molmed.2020.02.006
Katajisto, P., J. Döhla, C. L. Chaffer, N. Pentinmikko, N. Marjanovic, S. Iqbal, R. Zoncu, W. Chen, R. A. Weinberg, and D. M. Sabatini. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science. 348:340–343, 2015.
pubmed: 25837514
pmcid: 4405120
doi: 10.1126/science.1260384
Kim, C. A., and J. M. Berg. A 2.2 Å resolution crystal structure of a designed zinc finger protein bound to DNA. Nat. Struct. Biol. 3(11):940–945, 1996.
pubmed: 8901872
doi: 10.1038/nsb1196-940
Lagouge, M., and N. G. Larsson. The role of mitochondrial DNA mutations and free radicals in disease and ageing. J. Intern. Med. 273:529–543, 2013.
pubmed: 23432181
pmcid: 3675642
doi: 10.1111/joim.12055
Lee, H., S. Lee, G. Baek, A. Kim, B. C. Kang, H. Seo, and J. S. Kim. Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases. Nat. Commun. 12(1):1–6, 2021.
doi: 10.1038/s41467-020-20314-w
Lightowlers, R. N., P. F. Chinnery, D. M. Turnbull, N. Howell, and D. M. Turnbuu. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet. 13:450–455, 1997.
pubmed: 9385842
doi: 10.1016/S0168-9525(97)01266-3
Liu, X., C. N. Kim, J. Yang, R. Jemmerson, and X. Wang. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 86:147–157, 1996.
pubmed: 8689682
doi: 10.1016/S0092-8674(00)80085-9
Mani, M., K. Kandavelou, F. J. Dy, S. Durai, and S. Chandrasegaran. Design, engineering, and characterization of zinc finger nucleases. Biochem. Biophys. Res. Commun. 335:447–457, 2005.
pubmed: 16084494
doi: 10.1016/j.bbrc.2005.07.089
McCully, J. D., D. B. Cowan, S. M. Emani, and P. J. del Nido. Mitochondrial transplantation: from animal models to clinical use in humans. Mitochondrion. 2017. https://doi.org/10.1016/j.mito.2017.03.004 .
doi: 10.1016/j.mito.2017.03.004
pubmed: 28342934
Minczuk, M., M. A. Papworth, P. Kolasinska, M. P. Murphy, and A. Klug. Sequence-specific modification of mitochondrial DNA using a chimeric zinc finger methylase. Proc. Natl. Acad. Sci. USA. 103:19689, 2006.
pubmed: 17170133
pmcid: 1750892
doi: 10.1073/pnas.0609502103
Minczuk, M., M. A. Papworth, J. C. Miller, M. P. Murphy, and A. Klug. Development of a single-chain, quasi-dimeric zinc-finger nuclease for the selective degradation of mutated human mitochondrial DNA. Nucleic Acids Res. 36:3926–3938, 2008.
pubmed: 18511461
pmcid: 2475635
doi: 10.1093/nar/gkn313
Mingozzi, F., and K. A. High. Overcoming the Host Immune Response to Adeno-Associated Virus Gene Delivery Vectors: The Race Between Clearance, Tolerance, Neutralization, and Escape. Annu. Rev. Virol. 4:511–534, 2017.
pubmed: 28961410
doi: 10.1146/annurev-virology-101416-041936
Mok, B. Y., M. H. de Moraes, J. Zeng, D. E. Bosch, A. V. Kotrys, A. Raguram, F. S. Hsu, M. C. Radey, S. B. Peterson, V. K. Mootha, J. D. Mougous, and D. R. Liu. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature. 583(7817):631–637, 2020.
pubmed: 32641830
pmcid: 7381381
doi: 10.1038/s41586-020-2477-4
Moretton, A., F. Morel, B. Macao, P. Lachaume, L. Ishak, M. Lefebvre, I. Garreau-Balandier, P. Vernet, M. Falkenberg, and G. Farge. Selective mitochondrial DNA degradation following double-strand breaks. PLoS ONE. 12:e0176795, 2017.
pubmed: 28453550
pmcid: 5409072
doi: 10.1371/journal.pone.0176795
Moscou, M. J., and A. J. Bogdanove. A simple cipher governs DNA recognition by TAL effectors. Science. 326:1501, 2009.
pubmed: 19933106
doi: 10.1126/science.1178817
Nissanka, N., and C. T. Moraes. Mitochondrial DNA heteroplasmy in disease and targeted nuclease-based therapeutic approaches. EMBO Rep. 21:e49612, 2020.
pubmed: 32073748
pmcid: 7054667
doi: 10.15252/embr.201949612
Park, C. B., and N. G. Larsson. Mitochondrial DNA mutations in disease and aging. J. Cell Biol. 193:809–818, 2011.
pubmed: 21606204
pmcid: 3105550
doi: 10.1083/jcb.201010024
Peeva, V., D. Blei, G. Trombly, S. Corsi, M. J. Szukszto, P. Rebelo-Guiomar, P. A. Gammage, A. P. Kudin, C. Becker, J. Altmüller, M. Minczuk, G. Zsurka, and W. S. Kunz. Linear mitochondrial DNA is rapidly degraded by components of the replication machinery. Nat. Commun. 9(1):1–11, 2018.
doi: 10.1038/s41467-018-04131-w
Pereira, C. V., S. R. Bacman, T. Arguello, U. Zekonyte, S. L. Williams, D. R. Edgell, and C. T. Moraes. mitoTev-TALE: a monomeric DNA editing enzyme to reduce mutant mitochondrial DNA levels. EMBO Mol. Med. 10:e8084, 2018.
pubmed: 30012581
pmcid: 6127889
doi: 10.15252/emmm.201708084
Persikov, A. V., J. L. Wetzel, E. F. Rowland, B. L. Oakes, D. J. Xu, M. Singh, and M. B. Noyes. A systematic survey of the Cys2His2 zinc finger DNA-binding landscape. Nucleic Acids Res. 43:1965–1984, 2015.
pubmed: 25593323
pmcid: 4330361
doi: 10.1093/nar/gku1395
Pingoud, A., G. G. Wilson, and W. Wende. Type II restriction endonucleases—a historical perspective and more. Nucleic Acids Res. 42:7489–7527, 2014.
pubmed: 24878924
pmcid: 4081073
doi: 10.1093/nar/gku447
Poulton, J., M. R. Chiaratti, F. V. Meirelles, S. Kennedy, D. Wells, and I. J. Holt. Transmission of mitochondrial DNA diseases and ways to prevent them. PLoS Genet. 6:e1001066, 2010.
pubmed: 20711358
pmcid: 2920841
doi: 10.1371/journal.pgen.1001066
Rahman, S., J. Poulton, D. Marchington, and A. Suomalainen. Decrease of 3243 A–>G mtDNA mutation from blood in MELAS syndrome: a longitudinal study. Am. J. Hum. Genet. 68:238–240, 2001.
pubmed: 11085913
doi: 10.1086/316930
Reddy, P., A. Ocampo, K. Suzuki, J. Luo, S. R. Bacman, S. L. Williams, A. Sugawara, D. Okamura, Y. Tsunekawa, J. Wu, D. Lam, X. Xiong, N. Montserrat, C. R. Esteban, G. H. Liu, I. Sancho-Martinez, D. Manau, S. Civico, F. Cardellach, M. Del Mar O’Callaghan, J. Campistol, H. Zhao, J. M. Campistol, C. T. Moraes, and J. C. Izpisua Belmonte. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell. 161:459–469, 2015.
pubmed: 25910206
pmcid: 4505837
doi: 10.1016/j.cell.2015.03.051
Rossignol, R., B. Faustin, C. Rocher, M. Malgat, J. P. Mazat, and T. Letellier. Mitochondrial threshold effects. Biochem. J. 370:751–762, 2003.
pubmed: 12467494
pmcid: 1223225
doi: 10.1042/bj20021594
Sallevelt, S. C. E. H., J. C. F. M. Dreesen, M. Drüsedau, S. Spierts, E. Coonen, F. H. J. van Tienen, R. J. T. van Golde, I. F. M. de Coo, J. P. M. Geraedts, C. E. M. de Die-Smulders, and H. J. M. Smeets. Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success. J. Med. Genet. 50:125–132, 2013.
pubmed: 23339111
doi: 10.1136/jmedgenet-2012-101172
Santorelli, F. M., K. Tanji, S. Shanske, and S. DiMauro. Heterogeneous clinical presentation of the mtDNA NARP/T8993G mutation. Neurology. 49:270–273, 1997.
pubmed: 9222207
doi: 10.1212/WNL.49.1.270
Shokolenko, I. N., and M. F. Alexeyev. Mitochondrial DNA: a disposable genome? Biochim. Biophys. Acta. 1852:1805, 2015.
pubmed: 26071375
pmcid: 4523420
doi: 10.1016/j.bbadis.2015.05.016
Shoubridge, E. A., and T. Wai. Mitochondrial DNA and the mammalian oocyte. Curr. Top. Dev. Biol. 77:87–111, 2007.
pubmed: 17222701
doi: 10.1016/S0070-2153(06)77004-1
Skladal, D., J. Halliday, and D. R. Thorburn. Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain. 126:1905–1912, 2003.
pubmed: 12805096
doi: 10.1093/brain/awg170
Smith, J., M. Bibikova, F. G. Whitby, A. R. Reddy, S. Chandrasegaran, and D. Carroll. Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res. 28:3361, 2000.
pubmed: 10954606
pmcid: 110700
doi: 10.1093/nar/28.17.3361
Spinelli, J. B., and M. C. Haigis. The multifaceted contributions of mitochondria to cellular metabolism. Nat. Cell Biol. 20(7):745–754, 2018.
pubmed: 29950572
pmcid: 6541229
doi: 10.1038/s41556-018-0124-1
Suomalainen, A., and B. J. Battersby. Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nat. Rev. Mol. Cell Biol. 19(2):77–92, 2017.
pubmed: 28792006
doi: 10.1038/nrm.2017.66
Szczesny, R. J., M. S. Hejnowicz, K. Steczkiewicz, A. Muszewska, L. S. Borowski, K. Ginalski, and A. Dziembowski. Identification of a novel human mitochondrial endo-/exonuclease Ddk1/c20orf72 necessary for maintenance of proper 7S DNA levels. Nucleic Acids Res. 41:3144, 2013.
pubmed: 23358826
pmcid: 3597694
doi: 10.1093/nar/gkt029
Taylor, R. W., and D. M. Turnbull. Mitochondrial DNA mutations in human disease. Nat. Rev. Genet. 6:389–402, 2005.
pubmed: 15861210
pmcid: 1762815
doi: 10.1038/nrg1606
Tools | TAL Effector Nucleotide Targeter 2.0at. https://tale-nt.cac.cornell.edu/
Tuppen, H. A. L., E. L. Blakely, D. M. Turnbull, and R. W. Taylor. Mitochondrial DNA mutations and human disease. Biochim. Biophys. Acta – Bioenerg. 1797:113–128, 2010.
doi: 10.1016/j.bbabio.2009.09.005
Wallace, D. C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet. 39:359, 2005.
pubmed: 16285865
pmcid: 2821041
doi: 10.1146/annurev.genet.39.110304.095751
Wallace, D. C., G. Singh, M. T. Lott, J. A. Hodge, T. G. Schurr, A. M. S. Lezza, L. J. Elsas, and E. K. Nikoskelainen. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science. 242:1427–1430, 1988.
pubmed: 3201231
doi: 10.1126/science.3201231
Wang, D., P. W. L. Tai, and G. Gao. 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
Wanrooij, S., and M. Falkenberg. The human mitochondrial replication fork in health and disease. Biochim. Biophys. Acta. 1797:1378–1388, 2010.
pubmed: 20417176
doi: 10.1016/j.bbabio.2010.04.015
Wei, Y., Z. Li, K. Xu, H. Feng, L. Xie, D. Li, Z. Zuo, M. Zhang, C. Xu, H. Yang, and E. Zuo. Mitochondrial base editor DdCBE causes substantial DNA off-target editing in nuclear genome of embryos. Cell Discov. 8(1):1–4, 2022.
Yakes, F. M., and B. Van Houten. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc. Natl. Acad. Sci. USA. 94:514–519, 1997.
pubmed: 9012815
pmcid: 19544
doi: 10.1073/pnas.94.2.514
Yamada, Y., M. Ito, M. Arai, M. Hibino, T. Tsujioka, and H. Harashima. Challenges in promoting mitochondrial transplantation therapy. Int. J. Mol. Sci. 2020. https://doi.org/10.3390/ijms21176365 .
doi: 10.3390/ijms21176365
pubmed: 33327477
pmcid: 7764951
Yang, X., J. Jiang, Z. Li, J. Liang, and Y. Xiang. Strategies for mitochondrial gene editing. Comput. Struct. Biotechnol. J. 2021. https://doi.org/10.1016/j.csbj.2021.06.003 .
doi: 10.1016/j.csbj.2021.06.003
pubmed: 35035786
pmcid: 8733169
Yang, Y., H. Wu, X. Kang, Y. Liang, T. Lan, T. Li, T. Tan, J. Peng, Q. Zhang, G. An, Y. Liu, Q. Yu, Z. Ma, Y. Lian, B. S. Soh, Q. Chen, P. Liu, Y. Chen, X. Sun, R. Li, X. Zhen, P. Liu, Y. Yu, X. Li, and Y. Fan. Targeted elimination of mutant mitochondrial DNA in MELAS-iPSCs by mitoTALENs. Protein Cell. 9:283–297, 2018.
pubmed: 29318513
pmcid: 5829275
doi: 10.1007/s13238-017-0499-y
Zekonyte, U., S. R. Bacman, J. Smith, W. Shoop, C. V. Pereira, G. Tomberlin, J. Stewart, D. Jantz, and C. T. Moraes. Mitochondrial targeted meganuclease as a platform to eliminate mutant mtDNA in vivo. Nat. Commun. 12:1–11, 2021.
doi: 10.1038/s41467-021-23561-7
Zhang, H., S. P. Burr, and P. F. Chinnery. The mitochondrial DNA genetic bottleneck: inheritance and beyond. Essays Biochem. 62:225–234, 2018.
pubmed: 29880721
doi: 10.1042/EBC20170096