Induced Gene Therapy

Introduction

Telomeres are the ends of chromosomes that consist of tandem repeats of DNA sequences, with the length varying in various species. (Wong et al., 2008). The specific role of telomeres is to protect and guard the chromosomal ends from being damaged, and so if they become too short they lose their protective nature and leave the chromosomal ends exposed to damage (Wong et al. 2008). Types of damage that can be done to telomeres include degradation, recombination, as well as activities that repair DNA and may shorten the telomeres (Samper et al., 2001). The enzyme telomerase lengthens chromosome ends and restores length of the telomeres (Marion et al., 2009). Reengaging and reintroducing telomerase activity has been related to preventing

Bernardes de Jesus et al. have introduced gene therapy treatment in mice to view the effect that therapy will have on both adult (1 year old) and old (2 years old) mice, focusing on its effect on health, fitness, and aging. The proposed hypothesis states that induced gene therapy will have an impact on telomere length, thereby leading to positive results in both health and physiological aging. Conversely, the null hypothesis indicates that induced gene therapy will have no significant effect on the length of telomeres, indicating no change in health and physiological aging. The basis of this experiment centers around the notion that telomerase has the ability to grant rapid growth of cells in in vitro cells due to its capability to elongate the chromosomal telomere ends so that damage to these ends is prevented. In turn, reintroducing telomerase prevents premature stem cell malfunction through increased rates of telomere lengthening, which is enough to regress age-related health effects. The methodology involved in this study comprised of gene therapy involving adeno associated virus, AAV, which carries the cDNA of the telomerase gene Tert. Recombinant AAVs are frequently used in gene therapy practices due to their beneficial properties, some of which include their exceptional safety and non-integrative nature. This method also maintains long-term expression of genes in animal tissues with low proliferation rates of cells, showing why AAV is particularly useful in this study. There are several common factors that are associated with aging that can be combated through the use of AAV gene therapy as seen in this study. A common sign of aging present in mice is bone mineral density loss. In this study, mice that were treated with telomerase through AAV showed significantly higher bone mineral density 3-6 months after the