Aplastic anemia is a fatal bone marrow disorder characterized by peripheral 
pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired 
and develops at any stage of life. A subgroup of the inherited form is caused by 
replicative impairment of hematopoietic stem and progenitor cells due to very 
short telomeres as a result of mutations in telomerase and other telomere 
components. Abnormal telomere shortening is also described in cases of acquired 
aplastic anemia, most likely secondary to increased turnover of bone marrow stem 
and progenitor cells. Here, we test the therapeutic efficacy of telomerase 
activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying 
the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to 
short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of 
AAV9-Tert targets the bone marrow compartment, including hematopoietic stem 
cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues 
aplastic anemia and mouse survival compared with mice treated with the empty 
vector. Improved survival is associated with a significant increase in telomere 
length in peripheral blood and bone marrow cells, as well as improved blood 
counts. These findings indicate that telomerase gene therapy represents a novel 
therapeutic strategy to treat aplastic anemia provoked or associated with short 
telomeres.