Unlocking the Power of Artificial Chromosomes: A Breakthrough in Human Genetic Engineering

Tuesday - April 2 2024, 11:06 UTC - 7 months ago

Scientists have developed a more advanced method for creating artificial human chromosomes, opening the door to more effective gene therapies and a better understanding of how DNA works.

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.Since 1997, artificial genomes have become an established biotechnology. They’ve been used to rewrite DNA in bacteria, yeast, and plants, resulting in cells that can synthesize life-saving medications or eat plastic .

They could also help scientists better understand the functions of the mysterious DNA sequences littered throughout our genome.The technology also brought about the first synthetic organisms. In late 2023, scientists revealed yeast cells with half their genes replaced by artificial DNA—the team hopes to eventually customize every single chromosome. Earlier this year, another study reworked parts of a plant’s chromosome, further pushing the boundaries of synthetic organisms .

And by tinkering with the structures of chromosomes—for example, chopping off suspected useless regions—we can better understand how they normally function, potentially leading to treatments for diseases.The goal of building human artificial chromosomes isn’t to engineer synthetic human cells. Rather, the work is meant to advance gene therapy—delivering therapeutic genes to cells to cure disease. But doing so is currently fraught with problems .

In gene therapy, researchers use a vector (such as a virus or a nanoparticle) to carry their therapeutic gene into cells. But these vectors have limitations in terms of the amount of DNA they can carry. This makes it difficult to deliver large genes or multiple genes at once.Additionally, the vectors can trigger an immune response, leading to the rejection of the therapeutic gene. And once delivered, the gene can be turned off or fail to insert properly into the host cell’s DNA .

With the recent development from the University of Pennsylvania, scientists are hopeful that human artificial chromosomes could overcome these limitations and lead to more effective gene therapies.The potential for artificial chromosomes goes beyond just delivering therapeutic genes. They could also be used to introduce beneficial genetic material into cells, such as genes that protect against diseases like cancer or Alzheimer's .

Additionally, studying how artificial chromosomes interact with cells could provide valuable insights into how chromosomes naturally function in the human body.