A recent study demonstrates that CRISPR-based gene editing can selectively remove the extra copy of chromosome 21 in human cells. Published as a proof-of-concept study, the work highlights a method for chromosomal elimination that restores normal gene expression and cellular function in vitro.
Targeting the Extra Chromosome
Down syndrome results from trisomy 21, which involves the presence of an additional chromosome 21. Affecting approximately 1 in 700 live births, the condition is easily diagnosed early in development, yet no treatments exist beyond supportive care.
In this study, Ryotaro Hashizume and colleagues applied CRISPR-Cas9 technology to remove the additional chromosome in cultured cells. One of the key challenges in chromosome elimination is ensuring that the remaining pair consists of one maternal and one paternal copy. The researchers designed a CRISPR-based approach capable of distinguishing the extra chromosome, which enabled accurate cleavage without disrupting normal chromosomal pairs.
Chromosomal Elimination Restores Gene Expression
Hashizume’s team tested the method on trisomy 21 cell lines derived from both pluripotent stem cells and fibroblasts. In both cases, successful chromosome elimination led to the restoration of normal gene expression and cellular phenotypes. Suppressing the cell’s DNA repair mechanisms further increased the efficiency of chromosome removal.
While the technique proved effective in vitro, the authors acknowledge that there are limitations. The current approach sometimes alters the retained chromosomes, which presents a significant barrier to clinical applications. Additionally, in vivo feasibility remains uncertain.
Potential for Future Applications
Although not yet suitable for therapeutic use, the findings suggest that similar gene-editing strategies could eventually be adapted for neurons and glial cells. The ability to correct trisomy at the cellular level could lead to novel medical interventions for individuals with Down syndrome, but further research is required to refine the approach and assess its safety.
Publication Details
Ryotaro Hashizume, Sachiko Wakita, Hirofumi Sawada, Shin-ichiro Takebayashi, Yasuji Kitabatake, Yo****aka Miyagawa, Yoshifumi S Hirokawa, Hiroshi Imai, Hiroki Kurahashi, Trisomic rescue via allele-specific multiple chromosome cleavage using CRISPR-Cas9 in trisomy 21 cells, PNAS Nexus, Volume 4, Issue 2, February 2025, pgaf022, https://doi.org/10.1093/pnasnexus/pgaf022
Targeting the Extra Chromosome
Down syndrome results from trisomy 21, which involves the presence of an additional chromosome 21. Affecting approximately 1 in 700 live births, the condition is easily diagnosed early in development, yet no treatments exist beyond supportive care.
In this study, Ryotaro Hashizume and colleagues applied CRISPR-Cas9 technology to remove the additional chromosome in cultured cells. One of the key challenges in chromosome elimination is ensuring that the remaining pair consists of one maternal and one paternal copy. The researchers designed a CRISPR-based approach capable of distinguishing the extra chromosome, which enabled accurate cleavage without disrupting normal chromosomal pairs.
Chromosomal Elimination Restores Gene Expression
Hashizume’s team tested the method on trisomy 21 cell lines derived from both pluripotent stem cells and fibroblasts. In both cases, successful chromosome elimination led to the restoration of normal gene expression and cellular phenotypes. Suppressing the cell’s DNA repair mechanisms further increased the efficiency of chromosome removal.
While the technique proved effective in vitro, the authors acknowledge that there are limitations. The current approach sometimes alters the retained chromosomes, which presents a significant barrier to clinical applications. Additionally, in vivo feasibility remains uncertain.
Potential for Future Applications
Although not yet suitable for therapeutic use, the findings suggest that similar gene-editing strategies could eventually be adapted for neurons and glial cells. The ability to correct trisomy at the cellular level could lead to novel medical interventions for individuals with Down syndrome, but further research is required to refine the approach and assess its safety.
Publication Details
Ryotaro Hashizume, Sachiko Wakita, Hirofumi Sawada, Shin-ichiro Takebayashi, Yasuji Kitabatake, Yo****aka Miyagawa, Yoshifumi S Hirokawa, Hiroshi Imai, Hiroki Kurahashi, Trisomic rescue via allele-specific multiple chromosome cleavage using CRISPR-Cas9 in trisomy 21 cells, PNAS Nexus, Volume 4, Issue 2, February 2025, pgaf022, https://doi.org/10.1093/pnasnexus/pgaf022