Table 3 Preclinical studies on mitochondrial gene editing

From: Engineered mitochondria in diseases: mechanisms, strategies, and applications

Author	Diseases	Therapeutics	Delivery method	Animal model	Main result
Nervous system
Di, 2012⁴³⁵	Ethylmalonic acid encephalopathy	hETHE1 cDNA	ssAAV2/8 vector	Eth1 KO mice	Improvement of the disease’s primary metabolic and biochemical indicators
Reynaud-Dulaurier, 2020⁴³⁷	Leigh syndrome	Ndufs4-IRES	AAV9	Ndufs4 KO mice	Reduced gliosis, significant body weight and locomotor activity improvement, and a significantly prolonged survival time
Digestive system
Marta, 2021⁴³⁸	Mitochondrial neurogastrointestinal encephalomopathy	CRISPR/Cas9 and TYMP cDNA	Lipid nanoparticle or polymeric nanoparticle	Tymp/Upp1 mice	Promoted the synthesis and secretion of TYMP mRNA and active enzymes in the liver
Battani, 2014⁴³⁹	Mitochondrial hepatocerebral disease	MPV17	AAV8	MPV17 KO mice	The supramolecular complex level of MPV17 was effectively restored, and the progression of liver failure was delayed
Musculoskeletal system
Flierl, 2005⁴⁴¹	Mitochondrial myopathy	ANT1 cDNA	AAV2	ANT1 KO mice	Improved mitochondrial functions and reversed histopathological and clinical symptom changes
Perdomini, 2014⁴⁷³	Friedreich’s ataxia	hFXN cDNA	AAVrh10	Mck-Cre-Fxn^L3/L– mice	Improved frataxin protein expression, delayed the progression of myocardial fibrosis, and prolonged the survival time
Myocardial disease
Bacman, 2018¹¹⁵	Mitochondrial cardiomyopathy	mitoTALENs	AAV9	m.50624 C > T mice	Restored the normal expression of tRNA^Ala, and ameliorated the symptoms of mitochondrial cardiomyopathy.
Gammage, 2018¹⁴⁶	Mitochondrial cardiomyopathy	mitoZFNs	AAV9.45	m.50624 C > T mice	Restored mitochondrial tRNA^Ala expression levels in the heart and improved tissue levels of lactate, pyruvate, and aspartate
Zekonyte, 2021⁷⁰	Mitochondrial cardiomyopathy	mitoARCUS	AAV9	m.50624 C > T mice	Reduced the amount of mutant mtDNA in organs by inducing specific dsDNA breaks

AAV adeno-associated viruses, ANT1 adenine nucleotide translocator 1, Cas9 CRISPR-associated protein 9, CRISPR clustered regularly interspaced short palindromic repeats, hETHE1 human ethylmalonic encephalopathy protein 1, hFXN human frataxin, IRES intra-ribosome-entry-site, KO knockout, mitoARCUS mitochondrial-targeted meganuclease, mitoTALENs mitochondrial-targeted transcription activator-like effector nucleases, mitoZFNs mitochondrial-targeted zinc finger nucleases, Ndufs4 ubiquinone oxidoreductase subunit S4, TYMP thymidine phosphorylase, Upp1 uridine phosphorylase 1

Back to article page

Table 3 Preclinical studies on mitochondrial gene editing

Search

Quick links