Table 2.

Summary of potential therapeutic effects expected by targeting mt-NAs.

Associated diseases	mt-NA-mediated therapeutic effects
	Target	Potential therapeutic effects
SARS-CoV-2	STING36	STING inhibition reduces SARS-CoV-2-induced inflammation in mice.
	TLR945	Targeting TLR9 rescues compromised endothelial cell function due to reduced expression of nitric oxide synthase.
Non-alcoholic steatohepatitis	STING38	STING functions as an mtDNA sensor in KCs of the liver under lipid overload to induce NF-κB-dependent inflammation in the context of NASH.
Acute kidney injury	cGAS-STING40	Reduced activation of the cGAS-STING pathway prevents cytosolic mtDNA-mediated inflammation in cisplatin-induced AKI.
Rheumatoid arthritis	cGAS-STING41	cGAS deficiency ameliorates arthritic symptoms and reduces ISG induction.
	NLRP3 inflammasome51	Targeting NLRP3 or downstream caspases suppresses IL-1 production in the RA context.
Amyotrophic lateral sclerosis	cGAS-STING42	cGAS and STING inhibitors prevent TDP-43-induced inflammation and improve the symptoms of neuronal decline in patients with diseases involving TDP-43 proteinopathy.
Liver disease	TLR327	Targeting mt-dsRNA-mediated TLR3 activation prevents the recruitment of γδ T cells and expression of IL‐17A in the early stage of ALD.
	HSP6061	Overexpression of HSP60 significantly reduces weight gain and fat accumulation in adipose tissue as well as mt-dsRNA-mediated inflammation in chronic kHFD.
Osteoarthritis	POLRMT26	Reduced expression of mt-dsRNAs by 2-CM treatment rescues the activation of PKR and eIF2α and reduces ISG induction.
Sjögren’s disease	POLRMT57	Downregulation of mtRNAs reduces the phosphorylation of PKR and attenuates ISG induction, which rescues the viability of salivary gland acinar cells.