Nucleic acid prodrugs

1. A method of treating a mitochondrial DNA depletion syndrome, comprising administering to a patient a therapeutically-effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein:

R 1 is C 5-14 aryl or mono, bi, or tricyclic heteroaryl;

R 2 and R 2 ′, each independently, are hydrogen, alkyl or aralkyl;

R 3 is alkyl or aralkyl;

R 4 is hydrogen or alkyl; and

NT is a nucleobase;

and further wherein, the mitochondrial DNA depletion syndrome is DGUOK deficiency.

2. The method of claim 1 , wherein the mitochondrial DNA depletion syndrome is DGUOK deficiency, and NT is 9-adeninyl or 9-guaninyl.

3. The method of claim 1 , wherein the mitochondrial DNA depletion syndrome is DGUOK deficiency, and NT is 9-adeninyl or 9-guaninyl or a 9-adeninyl or 9-guaninyl prodrug moiety.