Cited by 249Mitochondrial Function and PathologyDNA and Nucleic Acid ChemistryRNA Interference and Gene Delivery

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Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleic acids

Taylor, Robert W., Chinnery, Patrick F., Turnbull, Douglass M., Lightowlers, Robert N.·1997·Nature Genetics

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Abstract

Mitochondrila DNA (mtDNA) is the only extrachromosomal DNA in humans. It is a small (16.5 kb) genome which encodes 13 essential peptides of the respiratory chain, two rRNAs and 22 tRNAs. Defects of this genome are now recognized as important causes of disease and may take the form of point mutations or rearrangements. There is no effective treatment for patients with mtDNA mutations. In the majority of patients with mtDNA defects, both mutant and wild-type molecules are present in the same cell-a phenomenon known as intracellular heteroplasmy. In addition, in the presence of heteroplasmy there is a threshold whereby a certain level of mutant mtDNA is necessary before the disease becomes biochemically and clinically apparent. Based on the presence of heteroplasmy and the recessive nature of these mutations, we believe it will be possible to treat patients by selectively inhibiting the replication of the mutant mtDNA, thereby allowing propagation of only the wild-type molecule. To confirm the validity of such an approach we synthesised peptide nucleic acids (PNAs) complementary to human mtDNA templates containing a deletion breakpoint or single base mutation, both mutations well documented to cause disease. Using an in vitro replication run-off assay under physiological conditions, the antigenomic PNAs specifically inhibited replication of mutant but not wild-type mtDNA templates. Furthermore, we have shown uptake of these PNAs into cultured human myoblasts. We believe that we have therefore established the potential value of antigenomic PNA therapy for patients with heteroplasmic mtDNA disorders.

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DNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572
Sequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,740
Sequence-Selective Recognition of DNA by Strand Displacement with a Thymine-Substituted Polyamide
Nielsen, P. E., Egholm, M., Berg, R. H., & Buchardt, O. (1991) · Science · doi:10.1126/science.1962210 · Cited by 3,332
PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules
Egholm, M., Buchardt, O., Christensen, L., Behrens, C., Freier, S. M., Driver, D. A., Berg, R. H., Kim, S. K., Norden, B., & Nielsen, P. E. (1993) · Nature · doi:10.1038/365566a0 · Cited by 2,079
Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies
Holt, I. J., Harding, A. E., & MORGAN-HUGHES, J. A. (1988) · Nature · doi:10.1038/331717a0 · Cited by 1,860
Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation
Shoffner, J. M., Lott, M. T., Lezza, A. M. S., Seibel, P., Ballinger, S. W., & Wallace, D. C. (1990) · Cell · doi:10.1016/0092-8674(90)90059-n · Cited by 1,476
Diseases of the mitochondrial DNA
Wallace, D. C. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.005523 · Cited by 1,319
Mitochondrial Genetics: A Paradigm for Aging and Degenerative Diseases?
Wallace, D. C. (1992) · Science · doi:10.1126/science.1533953 · Cited by 1,262
Mitochondrial DNA Deletions in Progressive External Ophthalmoplegia and Kearns-Sayre Syndrome
Moraes, C. T., DiMauro, S., Zeviani, M., Lombès, A., Shanske, S., Miranda, A. F., Nakase, H., Bonilla, E., Werneck, L. C., Servidei, S., et al. (1989) · New England Journal of Medicine · doi:10.1056/nejm198905183202001 · Cited by 1,029
Stability of peptide nucleic acids in human serum and cellular extracts
Demidov, V. V., Potaman, V. N., Frank-Kamenetskii, M. D., Egholm, M., Buchard, O., Sönnichsen, S. H., & Nlelsen, P. E. (1994) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)90171-6 · Cited by 749

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Background
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BackgroundMethodInfluential
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Background
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Background
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Background
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Background
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Background
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“was demonstrated using peptide nucleic acids (PNAs) [157].”
BackgroundMethod
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“[90] proposed a strategy that aimed to specifically block the replication of the mutant mtDNA by peptide nucleic acid (PNA), thereby allowing the selective propagation of the wild-type DNA.”
Background
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Thyagaraiani, D., & Byrne, E. (2002) · International review of neurobiology · doi:10.1016/s0074-7742(02)53005-1 · Cited by 6
Enhanced annealing of mismatched oligonucleotides using a novel melting curve assay allows efficient in vitro discrimination and restriction of a single nucleotide polymorphism
Doyle, S. R., Chan, C. K., & Grant, W. N. (2011) · BMC Biotechnology · doi:10.1186/1472-6750-11-83 · Cited by 5
“This mutation was chosen as a target as it is one of the most common pathological mtDNA heteroplasmic variants affecting mt-tRNA synthesis [8] and that PNA sequence discrimination of this SNP has been previously demonstrated [9-11].”
Background
Bridging PNAs can bind preferentially to a deleted mitochondrial DNA template but replication by mitochondrial DNA polymerase γ in vitro is not impaired
McGregor, A., Smith, P., Roß, G., Taylor, R. W., Turnbull, D. M., & Lightowlers, R. N. (2003) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/j.bbaexp.2003.08.005 · Cited by 5
Mitochondrial DNA common deletion in cancer: Emerging evidence and methodological challenges
Ho, M. K., & Ho, J. W. K. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.09.010 · Cited by 4
“First proposed in 1997, the use of synthetic peptide nucleic acids (PNAs) designed to be complementary to human mtDNA carrying the CD was proposed to inhibit the replication of CD-mtDNA [31].”
Targeting Mitochondria: Innovation from Mitochondrial Drug Delivery System (DDS) to Mitochondrial Medicine
Yamada, Y., & Harashima, H. (2012) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.12-00220-4 · Cited by 4
Medicinal chemistry of plasmid DNA with peptide nucleic acids: A new strategy for gene therapy
Zelphati, O., Felgner, J. H., Wang, Y., Liang, X., Wang, X., & Felgner, P. L. (2003) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-004-4906-x · Cited by 4
“They have been used as artificial transcription promoters, artificial pseudo-restriction enzymes, DNA markers for electron microscopy, and for their antiviral and antitumor activity [34, 38, 41-45 ].”
Method
ClickIn: a flexible protocol for quantifying mitochondrial uptake of nucleobase derivatives
Hoogewijs, K., James, A. M., Smith, R. A. J., Abendroth, F., Gait, M. J., Murphy, M. P., & Lightowlers, R. N. (2017) · Interface Focus · doi:10.1098/rsfs.2016.0117 · Cited by 4
“To facilitate selective binding to the mutated molecule, nucleobase derivatives such as peptide nucleic acids (PNAs) were used [5].”
Method
Tipping the scales in favour of mitochondrial gene therapy
Bigger, B., Collombet, J.-M., & Coutelle, C. C. (1999) · Gene Therapy · doi:10.1038/sj.gt.3301090 · Cited by 4
MERRF and MELAS: current gene therapy trends and approaches
Agresti, C. A., Halkiadakis, P. N., & Tolias, P. P. (2018) · Journal of Translational Genetics and Genomics · doi:10.20517/jtgg.2018.05 · Cited by 4
“, 2016 Taylor et al .([54]), 1997 Chang et al .”
BackgroundMethodInfluential
Recent developments in mitochondrial medicine (part 2)
Weissig, V., & Edeas, M. A. (2022) · 4open · doi:10.1051/fopen/2022002 · Cited by 3
Mitochondrial Medicine in Health and Disease: Interface Between Athletic Performance and Therapeutics
Wallace, D. C. (2010) · Wiley eBooks · doi:10.1002/9781444327335.ch2 · Cited by 3
The Use of Fibroblasts from Patients with Inherited Mitochondrial Disorders for Pathomechanistic Studies and Evaluation of Therapies
Soiferman, D., & Saada, A. (2015) · Wiley eBooks · doi:10.1002/9781119017127.ch18 · Cited by 3
Mitochondrial Function and Neurodegenerative Diseases
Wilkins, H. M., Weidling, I., Koppel, S., Wang, X., von Schulze, A., & Swerdlow, R. H. (2018) · The Molecular and Cellular Basis of Neurodegenerative Diseases · doi:10.1016/b978-0-12-811304-2.00013-4 · Cited by 2
Pathologies de l’ADN mitochondrial et stratégies thérapeutiques
Tonin, Y., & Entelis, N. (2014) · médecine/sciences · doi:10.1051/medsci/20143012013 · Cited by 2
Peptide Nucleic Acids as Agents to Modify Target Gene Expression and Function
Wang, G., & Glazer, P. M. (2007) · Springer eBooks · doi:10.1007/0-387-32956-0_14 · Cited by 2
Modulation of nucleic acid information processing by PNAs: potential use in anti-viral therapeutics
Bastide, L., Lebleu, B., & Robbins, I. J. (2003) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-004-4923-9 · Cited by 2
Blockade of Plasmid Replication Mediated by Peptide Nucleic Acids
Liebling, M. R., Jou, N. T., Fang, W., & Louie, J. S. (2003) · Molecular Biotechnology · doi:10.1385/mb:25:3:229 · Cited by 2
“PNAs also have been reported to block the action of some DNA polymerases, again in vitro (6, 7 ).”
Background
Mitochondrial DNA-related disorders: emphasis on mechanisms and heterogeneity
Cagin, U., & Enrı́quez, J. A. (2015) · TURKISH JOURNAL OF BIOLOGY · doi:10.3906/biy-1505-20 · Cited by 2
“The primary goal for an effective gene therapy of mtDNA-related diseases is to alter the level of heteroplasmy, either by targeted degradation of mutant mtDNA or by blocking replication (Taylor et al., 1997).”
Background
Dysfunction of Mitochondrial ATP Production As a Target for Personalized Cancer Therapy
Tsuneoka, M., Teye, K., Okamoto, K., & Tanaka, Y. (2009) · Current pharmacogenomics and personalized medicine (Online)/Current pharmacogenomics and personalized medicine · doi:10.2174/187569209787582358 · Cited by 2
PNAs as novel cancer therapeutics
Mologni, L., & Gambacorti-Passerini, C. B. (2003) · International Journal of Peptide Research and Therapeutics · doi:10.1007/bf02484565 · Cited by 2
Future of Post-Genomic Cardiology
Marı́n-Garcı́a, J. (2007) · Elsevier eBooks · doi:10.1016/b978-012373698-7/50020-6 · Cited by 2
Creatine Supplementation in Mitochondrial Cytopathies
Bourgeois, J. M., & Tarnopolsky, M. A. (2000) · Medical science symposia series · doi:10.1007/978-94-011-4237-3_12 · Cited by 2
Treatment of Mitochondrial Diseases
DiMauro, S. (2002) · Springer eBooks · doi:10.1007/978-2-8178-0929-8_26 · Cited by 2
Implications of mtDNA in human health and diseases
Seethashankar, S., Hariharan, S., & Parvathi, V. D. (2025) · Biotechnologia · doi:10.5114/bta/204532 · Cited by 1
“This has been demonstrated using an in vitro replication run-off assay (Taylor et al. 1997).”
Epilepsies Due to Monogenic Disorders of Metabolism
Depondt, C. (2009) · Blue books of neurology · doi:10.1016/b978-1-4160-6171-7.00011-x · Cited by 1
Mitochondrial Therapeutic Approaches in Parkinson’s Disease
Esteves, A. R., Silva, D. F., G-Fernandes, M., Gomes, R., & Cardoso, S. M. (2016) · Springer eBooks · doi:10.1007/978-3-319-42139-1_9 · Cited by 1
Current Perspectives of Mitochondrial Dysfunction and Associated Diseases
Gupta, N. (2016) · MOJ Cell Science & Report · doi:10.15406/mojcsr.2016.03.00043
The use of PNAs and their derivatives in mitochondrial gene therapy
Smith, P., Ross, G. F., Wardell, T. M., Taylor, R. W., Turnbull, D. M., & Lightowlers, R. N. (2003) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-004-4901-2 · Cited by 1
“Previously, we were able to show that a short 11-mer PNA which spans the A8344G mutation known to cause MERRF (myoclonus, epilepsy with ragged red fibres) demonstrates binding selectivity to a template carrying the MERRF mutation and not a template identical except for a single nucleotide [18].”
BackgroundMethod

Authors: Taylor, R. W., Chinnery, P. F., Turnbull, D. M., & Lightowlers, R. N.
Affiliations: Newcastle University (GB)
Corresponding author: Turnbull, Douglass M.
ORCID: Taylor, Robert W.
Chinnery, Patrick F.
Turnbull, Douglass M.
Lightowlers, Robert N.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1997-02
Volume: 15
Issue: 2
Pages: 212-215
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng0297-212
OpenAlex: W1964789697
Cited by: 249
References: 31
Citations by year: 2025: 5 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 9 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 6 · 2013: 2 · 2012: 10
FWCI: 5.65
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords: mitochondrial DNA, mitochondrial DNA replication, peptide nucleic acid, heteroplasmy, myoblasts, mitochondrial disease, deletion breakpoints, single-base mutations
MeSH terms: Cell Line, Depression, Chemical, DNA Replication, DNA, Mitochondrial, DNA, Single-Stranded, Humans, Mitochondria, Muscle, Oligodeoxyribonucleotides, Peptides, Templates, Genetic, Drug Design, MERRF Syndrome

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Selective inhibition of mutant human mitochondrial DNA replication in vitro by peptide nucleic acids

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