Hutchinson-Gilford progeria syndrome, a rare progressive genetic disorder, contributes to advanced premature aging and affects approximately 400 people worldwide. Children affected by this genetic mutation have an average life expectancy of only 14 years and suffer debilitating complications associated with aging including stunted growth, stiff joints, bone disease, and cardiac complications. A collaboration of scientists from Harvard, Brown, and Vanderbilt have discovered a revolutionary gene editor, similar to CRISPR, that corrects the progeria mutation in mice. These results indicate the vast potential of gene editors for progeria and other genetic conditions.
The research team developed a gene editor to swap out a single base pair that leads to the progeria mutation. DNA base pairs are the fundamental unit composing the DNA structure. There are four unique bases each with a matching pair, and a mismatch of these pairs can generate genetic mutations. The mutated base pairs in progeria patients prevent the production of the critical protein Lamin A, which supports the membrane that creates the cellular nucleus. The gene editor swaps out the incorrect base pair for the correct one, which allows the cells to produce Lamin A. The gene editor was able to be directly injected into affected mice, allowing their bodies to correct the mutation and prevent continued degeneration due to progeria.
Thus far, the gene editor has only been experimentally attempted in cells and mice, although with impressive results. Cultured cells from two progeria patients were first used to examine the potential DNA base editing. Upon successful cellular culture with minimal unwanted effects, the research team experimented with living mouse subjects. Lamin A levels rose throughout several different tissue systems, with correction of the mutation in 20% to 60% of affected cells across various organ systems six months after injection. A single injection not only increased Lamin A production, but also drastically increased the longevity of the affected mice to twice the normal lifespan of a mouse with progeria. These results have been critically acclaimed with high hopes to start clinical human trials and potentially eradicate this debilitating condition.
First author Luke Koblan is a graduate student studying chemical biology at the Harvard University Department of Chemistry and Chemical Biology.
Managing Correspondent: Samantha Tracy
Press Article: “‘Incredible’ gene-editing result in mice inspires plans to treat premature-aging syndrome in children”, Science Magazine
Original Journal Article: “In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice”, Nature
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