Synergistic Deoxynucleoside and Gene Therapies for Thymidine Kinase 2 Deficiency.

ABSTRACT:

Objective

Autosomal recessive human thymidine kinase 2 (TK2) mutations cause TK2 deficiency, which typically manifests as a progressive and fatal mitochondrial myopathy in infants and children. Treatment with pyrimidine deoxynucleosides deoxycytidine and thymidine ameliorates mitochondrial defects and extends the lifespan of Tk2 knock-in mouse (Tk2^KI ) and compassionate use deoxynucleoside therapy in TK2 deficient patients have shown promising indications of efficacy. To augment therapy for Tk2 deficiency, we assessed gene therapy alone and in combination with deoxynucleoside therapy in Tk2^KI mice.

Methods

We generated pAAVsc CB6 PI vectors containing human TK2 cDNA (TK2). Adeno-associated virus (AAV)-TK2 was administered to Tk2^KI , which wer

SUBMITTER: Lopez-Gomez C 

PROVIDER: S-EPMC9307066 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature