Down syndrome is a genetic disorder caused by trisomy of chromosome 21, where an individual has an extra copy of chromosome 21. As result of which there is over expression of genes like DYRK1A, APP, etc. leading to development of congenital anomalies, intellectual disability and increased risk of conditions like Alzheimer’s disease.
Current clinical advances in CRISPR-Cas9 gene editing have opened the possibility of targeting the extra chromosome itself.
What exactly is CRISPR:
CRISPR-Cas9 is a genome editing tool that, uses guide RNA (gRNA) to identify a specific DNA sequence. Thereafter, Cas9 enzyme is used to cut DNA at that location.
In case of Down syndrome, scientists are attempting to remove the entire extra chromosome 21.
Recent research studies have demonstrated that CRISPR can target the third copy of chromosome 21 specifically, Induce multiple DNA breaks in that chromosome and cause the extra chromosome to become unstable and get eliminated during cell division. This process is called trisomy rescue.
Despite promising results, risks of off target DNA damage affecting normal chromosomes and ethical concerns like genetic modification of embryos are limiting the clinical applicability of this technology in Down syndrome.
While still experimental, this research represents a major leap towards chromosome level therapy.