Human Artificial Chromosomes Could Ferry Tons More DNA Cargo Into Cells

by Shelly Fan at Singularity Hub: The human genetic blueprint is deceptively simple. Our genes are tightly wound into 46 X-shaped structures called chromosomes. Crafted by evolution, they carry DNA and replicate when cells divide, ensuring the stability of our genome over generations.

In 1997, a study torpedoed evolution’s playbook. For the first time, a team created an artificial human chromosome using genetic engineering. When delivered into a human cell in a petri dish, the artificial chromosome behaved much like its natural counterparts. It replicated as cells divided, leading to human cells with 47 chromosomes.

Rest assured, the goal wasn’t to artificially evolve our species. Rather, artificial chromosomes can be used to carry large chunks of human genetic material or gene editing tools into cells. Compared to current delivery systems—virus carriers or nanoparticles—artificial chromosomes can incorporate far more synthetic DNA.

In theory, they could be designed to ferry therapeutic genes into people with genetic disorders or add protective ones against cancer.

Yet despite over two decades of research, the technology has yet to enter the mainstream. One challenge is that the short DNA segments linking up to form the chromosomes stick together once inside cells, making it difficult to predict how the genes will behave.

This month, a new study from the University of Pennsylvania changed the 25-year-old recipe and built a new generation of artificial chromosomes. Compared to their predecessors, the new chromosomes are easier to engineer and use longer DNA segments that don’t clump once inside cells. They’re also a large carrier, which in theory could shuttle genetic material roughly the size of the largest yeast chromosome into human cells.

“Essentially, we did a complete overhaul of the old approach to HAC [human artificial chromosome] design and delivery,” study author Dr. Ben Black said in a press release.

“The work is likely to reinvigorate efforts to engineer artificial chromosomes in both animals and plants,” wrote the University of Georgia’s Dr. R. Kelly Dawe, who was not involved in the study.

More here.