Telomerase gene therapy for fibrosis


Dr. Maria Blasco is the leader of the CNIO (Centro Nacional de Investigaciones Oncológicas) and the leader of the Telomeres and Telomerase Group within the CNIO. The group studies the mechanisms by which tumor cells are immortal and normal cells are mortal. Immortality is one of the universal characteristics of cancer cells.

The enzyme telomerase is present in over 95% of all types of human cancers and is absent in normal cells in the body. Telomeres are nucleoprotein complexes located at the ends of chromosomes and are essential for chromosome protection and genomic stability, and progressive shortening of telomeres is associated with organism aging. As telomeres are shortened, adult stem cells experience reduced regenerative capacity and tissue repair ability, and maintenance becomes increasingly poor. We discuss telomeres and their role in aging in more detail here.

The Telomeres and Telomerase Group focus on the following areas of research:

  • Generating mouse models to validate telomeres and telomerase as therapeutic targets for cancer and age-related diseases.
  • Deciphering the interplay between telomeres and DNA repair pathways.
  • Studying the role and regulation of non-coding telomeric RNAs, or TERRA.
  • Testing telomerase gene therapy in ‘telomere syndromes’ and age-related diseases.
  • Elucidating the roles of telomerase and telomeres in adult stem cell biology and in the nuclear reprogramming of differentiated cells to iPS cells.

Dr. Blasco’s group has achieved an impressive amount of research in the last few years. In 2012, their publication captured public attention when they used pioneering telomerase gene therapy to reverse aspects of aging and increased the lifespan of mice[1]. Since then, the group has achieved a great deal, including demonstrating that telomerase therapy is able to reverse aplastic anemia[2] and reverse fibrosis in a very accurate mouse model of the disease they created in 2015 [3-4]. They have numerous publications, and a small summary here cannot do their work justice; we would suggest exploring their publications at the CNIO website to learn more.

Since 2018 the Blasco Lab has published two additional telomerase studies. A July 2019 study demonstrated that the telomere shortening rate predicts species lifespan in a variety of species  including mice, birds, goats, gulls, reindeer, vultures, Bottlenose dolphins, American flamingos, and Sumatran elephants [5]. A May 2021 study showed telomeres play a relevant role in allergen-induced airway inflammation. If is not clear if these studies will serve as preclinical work for any Phase I clinical trials at this time[6].


[1] de Jesus, B. B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO molecular medicine, 4(8), 691-704.
[2] Bär, C., Povedano, J. M., Serrano, R., Benitez-Buelga, C., Popkes, M., Formentini, I., … & Blasco, M. A. (2016). Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia. Blood, 127(14), 1770-1779.
[3] Povedano, J. M., Martinez, P., Flores, J. M., Mulero, F., & Blasco, M. A. (2015). Mice with pulmonary fibrosis driven by telomere dysfunction. Cell reports, 12(2), 286-299.
[4] Povedano, J. M., Martinez, P., Serrano, R., Tejera, Á., Gómez-López, G., Bobadilla, M., … & Blasco, M. A. (2018). Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres. eLife, 7, e31299.

[5] Whittemore, E. Vera, E. Martínez-Nevado, C. Sanpera, and M. A. Blasco, “Telomere shortening rate predicts species life span,” Proc. Natl. Acad. Sci., vol. 116, no. 30, pp. 15122–15127, Jul. 2019, doi: 10.1073/pnas.1902452116.

[6] Piñeiro-Hermida, S., Martínez, P. and Blasco, M.A. (2021), Short and dysfunctional telomeres protect from allergen-induced airway inflammation. Aging Cell, 20: e13352. https://doi.org/10.1111/acel.13352

Website: CNIO Telomeres and Telomerase Group

Articles: Researchers Cure Lung Fibrosis in Mice With a Single Gene Therapy