scholarly journals Corrigendum: Synergistic Deoxynucleoside and Gene Therapies for Thymidine Kinase 2 Deficiency

2022 ◽  
2020 ◽  
Author(s):  
Carlos Lopez-Gomez ◽  
Maria J. Sanchez-Quintero ◽  
Eung Jeon Lee ◽  
Gulio Kleiner ◽  
Jun Xie ◽  
...  

AbstractAutosomal recessive thymidine kinase 2 (TK2) mutations causes TK2 deficiency, which typically manifests as a progressive and fatal mitochondrial myopathy in infants and children. Treatment with deoxycytidine and thymidine ameliorates mitochondrial defects and extends lifespan of Tk2 knock-in mouse (TK2−/−); however, efficacy is limited by age- and tissue-dependent expression of the cytosolic enzymes Tk1 and Dck. Thus, therapies aimed at systemic restoration of TK2 activity are needed. Here, we demonstrate that delivery of human TK2 cDNA to Tk2−/− mice using AAV9 efficiently rescued Tk2 activity in all the tissues tested except kidney, delayed disease onset, and increased lifespan. Sequential treatment of Tk2−/− mice with AAV9 first followed by AAV2 at different ages allowed us to reduce the viral dose while further prolonging the lifespan. Furthermore, addition of deoxycytidine and deoxythymidine supplementation to AAV9 + AAV2 treated Tk2−/− mice dramatically improved mtDNA copy numbers in liver and kidney, animal growth, and lifespan. These data indicate that combined pharmacological and gene therapies may be highly efficacious for human TK2 deficiency.


2021 ◽  
Author(s):  
Carlos Lopez‐Gomez ◽  
Maria J. Sanchez‐Quintero ◽  
Eung Jeon Lee ◽  
Gulio Kleiner ◽  
Saba Tadesse ◽  
...  

2010 ◽  
Vol 33 (3) ◽  
pp. 231-236 ◽  
Author(s):  
Xiaoshan Zhou ◽  
Magnus Johansson ◽  
Nicola Solaroli ◽  
Björn Rozell ◽  
Alf Grandien ◽  
...  

2008 ◽  
Vol 28 (5) ◽  
pp. 797-820 ◽  
Author(s):  
María-Jesús Pérez-Pérez ◽  
Eva-María Priego ◽  
Ana-Isabel Hernández ◽  
Olga Familiar ◽  
María-José Camarasa ◽  
...  

1992 ◽  
Vol 206 (2) ◽  
pp. 485-490 ◽  
Author(s):  
Olof JANSSON ◽  
Christina BOHMAN ◽  
Birgitte MUNCH-PETERSEN ◽  
Staffan ERIKSSON

2012 ◽  
Vol 18 (20) ◽  
pp. 2981-2994 ◽  
Author(s):  
Eva-Maria Priego ◽  
Anna Karlsson ◽  
Federico Gago ◽  
Maria-Jose Camarasa ◽  
Jan Balzarini ◽  
...  

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