in Landmark Genetic Engineering Feat...
The study (Efficient formation of Single-copy Human Artificial Chromosomes), published in Science, describes an approach that,
Artificial chromosomes are lab-made structures designed to mimic the function of natural chromosomes, the packaged bundles of DNA found in the cells of humans and other organisms.
These synthetic constructs have the potential to serve as vehicles for delivering therapeutic genes or as tools for studying chromosome biology.
However, previous attempts to create HACs have been plagued by a major issue:
The Penn Medicine team, led by Dr. Ben Black, sought to overcome this challenge by completely overhauling the approach to HAC design and delivery.
To test their idea, the scientists turned to a tried-and-true workhorse of molecular biology: yeast.
They used a technique called transformation-associated recombination (TAR) cloning to assemble a whopping 750 kilobase DNA construct in yeast cells.
For context, that's about 25 times larger than the constructs used in previous HAC studies.
The construct contained DNA from both human and
bacterial sources, as well as sequences to help seed the formation
of the
centromere.
The results were stunning...
Furthermore,
But the researchers didn't stop there.
They also devised a clever way to visualize the HACs in their native, uncompacted state.
This allowed them to confirm that the HACs
maintained their single-copy status and circular topology, without
any unwanted rearrangements or additions.
HACs have the potential to serve as safer, more effective platforms for gene therapy compared to current virus-based delivery systems, which can trigger immune reactions and involve the risk of harmful viral DNA insertion into the host genome.
Artificial chromosomes also offer the
advantage of being able to carry much larger genetic payloads,
potentially allowing for the expression of entire gene networks or
complex protein machines.
While there is still work to be done to refine these artificial chromosomes and develop suitable delivery methods for therapeutic use, this study represents a significant leap forward in our ability to engineer designer genomes.
By providing a more efficient and controlled way
to construct HACs, the researchers have opened up exciting new
avenues for advancing synthetic biology and expanding the
toolkit for genetic manipulation.
This breakthrough not only brings us closer to realizing the full potential of gene therapy but also provides a powerful new platform for basic research into chromosome structure and function.
In the future, designer chromosomes may become a
standard part of the bioengineering arsenal, empowering scientists
to tackle a wide range of medical and agricultural challenges.
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