The Application Of CRISPR-Cas۹ In Down Syndrome Treatment: From Genetic Correction To Disease Modeling And Neurological Symptom Management: A Review

Down syndrome (DS), the most common chromosomal disorder caused by trisomy ۲۱, presents significant clinical complexities, including intellectual disability, congenital heart defects, and heightened risks of leukemia. Recent advancements in CRISPR-Cas۹ gene-editing technology offer promising therapeutic avenues for addressing the genetic underpinnings of DS. This review explores the multifaceted applications of CRISPR-Cas۹ in DS research, from silencing the extra chromosome ۲۱ to targeting specific genes like DYRK۱A and DSCAM to mitigate neurodevelopmental deficits. Notably, studies demonstrate the efficacy of allele-specific chromosome removal in induced pluripotent stem cells (iPSCs), achieving a ۱۳.۱% elimination rate with multiplexed guide RNAs. Additionally, CRISPR-Cas۹ has been instrumental in modeling DS-associated leukemias, such as acute myeloid leukemia (ML-DS) and acute lymphoblastic leukemia (ALL), by recapitulating mutations in GATA۱ and P۲RY۸-CRLF۲ fusions. The technology also elucidates the role of enhancer polymorphisms in IKZF۱ in B-cell dysfunction. Despite its potential, challenges like off-target effects, delivery efficiency, and ethical concerns remain. However, CRISPR-Cas۹’s precision in correcting gene dosage and chromosomal abnormalities positions it as a transformative tool for DS therapeutics. Future research must optimize safety and efficacy to transition these innovations into clinical applications, paving the way for personalized treatments for DS and related genetic disorders.

کلیدواژه ها:

CRISPR-Cas۹ ، Down syndrome (Trisomy ۲۱) ، Gene editing ، Acute Myeloid Leukemia (ML-DS) ، Neurodevelopmental impairments