Al-Zaidy, S. et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr. Pulmonol. 54, 179–185 (2019).

Article  PubMed  Google Scholar 

Russell, S. et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet 390, 849–860 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Thompson, A. A. et al. Gene therapy in patients with transfusion-dependent β-thalassemia. N. Engl. J. Med. 378, 1479–1493 (2018).

Article  CAS  PubMed  Google Scholar 

Kuzmin, D. A. et al. The clinical landscape for AAV gene therapies. Nat. Rev. Drug. Discov. 20, 173–174 (2021).

Article  CAS  PubMed  Google Scholar 

Iftikhar, M., Frey, J., Shohan, M. J., Malek, S. & Mousa, S. A. Current and emerging therapies for Duchenne muscular dystrophy and spinal muscular atrophy. Pharmacol. Ther. 220, 107719 (2021).

Article  CAS  PubMed  Google Scholar 

Gillmore, J. D. et al. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).

Article  CAS  PubMed  Google Scholar 

Gorman, G. S. et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann. Neurol. 77, 753–759 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gorman, G. S. et al. Mitochondrial diseases. Nat. Rev. Dis. Prim. 2, 16080 (2016).

Article  PubMed  Google Scholar 

Pitceathly, R. D. S., Keshavan, N., Rahman, J. & Rahman, S. Moving towards clinical trials for mitochondrial diseases. J. Inherit. Metab. Dis. 44, 22–41 (2021).

Article  PubMed  Google Scholar 

Rath, S. et al. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res 49, D1541–D1547 (2021).

Article  CAS  PubMed  Google Scholar 

Anderson, S. et al. Sequence and organization of the human mitochondrial genome. Nature 290, 457–465 (1981).

Article  CAS  PubMed  Google Scholar 

Gustafsson, C. M., Falkenberg, M. & Larsson, N. G. Maintenance and expression of mammalian mitochondrial DNA. Annu. Rev. Biochem. 85, 133–160 (2016).

Article  CAS  PubMed  Google Scholar 

Ng, Y. S. et al. Mitochondrial disease in adults: recent advances and future promise. Lancet Neurol. 20, 573–584 (2021).

Article  CAS  PubMed  Google Scholar 

Schon, E. A., Dimauro, S. & Hirano, M. Human mitochondrial DNA: roles of inherited and somatic mutations. Nat. Rev. Genet. 13, 878–890 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Larsson, N. G. & Clayton, D. A. Molecular genetic aspects of human mitochondrial disorders. Annu. Rev. Genet. 29, 151–178 (1995).

Article  CAS  PubMed  Google Scholar 

Rossignol, R. et al. Mitochondrial threshold effects. Biochem. J. 370, 751–762 (2003).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bugiardini, E. et al. Expanding the molecular and phenotypic spectrum of truncating MT-ATP6 mutations. Neurol. Genet. 6, e381 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pitceathly, R. D. S. et al. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease. Neurology 79, 1145–1154 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Banskota, S. et al. Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins. Cell 185, 250–265.e16 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Frangoul, H. et al. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N. Engl. J. Med. 384, 252–260 (2021).

Article  CAS  PubMed  Google Scholar 

Ribeil, J.-A. et al. Gene therapy in a patient with sickle cell disease. N. Engl. J. Med. 376, 848–855 (2017).

Article  CAS  PubMed  Google Scholar 

Mendell, J. R. et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 1713–1722 (2017).

Article  CAS  PubMed  Google Scholar 

Lundstrom, K. Viral vectors in gene therapy. Diseases 6, 42 (2018).

Article  PubMed Central  Google Scholar 

Crooke, S. T., Baker, B. F., Crooke, R. M. & Liang, X. H. Antisense technology: an overview and prospectus. Nat. Rev. Drug. Discov. 20, 427–453 (2021).

Article  CAS  PubMed  Google Scholar 

Silva-Pinheiro, P. & Minczuk, M. The potential of mitochondrial genome engineering. Nat. Rev. Genet. 23, 199–214 (2022).

Article  CAS  PubMed  Google Scholar 

Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824–844 (2020).

Article  CAS  PubMed  Google Scholar 

Scully, R., Panday, A., Elango, R. & Willis, N. A. DNA double-strand break repair-pathway choice in somatic mammalian cells. Nat. Rev. Mol. Cell Biol. 20, 698–714 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stewart, J. B. Current progress with mammalian models of mitochondrial DNA disease. J. Inherit. Metab. Dis. 44, 325–342 (2021).

Article  CAS  PubMed  Google Scholar 

King, M. P. & Attardi, G. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246, 500–503 (1989).

Article  CAS  PubMed  Google Scholar 

Brown, M. D., Trounce, I. A., Jun, A. S., Allen, J. C. & Wallace, D. C. Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber’s hereditary optic neuropathy mitochondrial DNA mutation. J. Biol. Chem. 275, 39831–39836 (2000).

Article  CAS  PubMed  Google Scholar 

Pallotti, F. et al. Biochemical analysis of respiratory function in cybrid cell lines harbouring mitochondrial DNA mutations. Biochem. J. 384, 287–293 (2004).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trounce, I., Neill, S. & Wallace, D. C. Cytoplasmic transfer of the mtDNA nt 8993 T->G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio. Proc. Natl Acad. Sci. USA 91, 8334–8338 (1994).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cavaliere, A., Marchet, S., Di Meo, I. & Tiranti, V. An in vitro approach to study mitochondrial dysfunction: a cybrid model. J. Vis. Exp. 181, e63452 (2022).

Google Scholar 

Kim, J., Koo, B. K. & Knoblich, J. A. Human organoids: model systems for human biology and medicine. Nat. Rev. Mol. Cell Biol. 21, 571–584 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, D., L Tai, P. W. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug. Discov. 18, 358–378 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Torres-Torronteras, J. et al. Long-term sustained effect of liver-targeted adeno-associated virus gene therapy for mitochondrial neurogastrointestinal encephalomyopathy. Hum. Gene Ther. 29, 708–718 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vila-Julià, F. et al. Efficacy of adeno-associated virus gene therapy in a MNGIE murine model enhanced by chronic exposure to nucleosides. EBioMedicine 62, 103133 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Torres-Torronteras, J. et al. Gene therapy using a liver-targeted AAV vector restores nucleoside and nucleotide homeostasis in a murine model of MNGIE. Mol. Ther. 22, 901–907 (2014).