$1.5 million for Khalil and colleagues to realize dream of human artificial chromosomes
The Chan Zuckerberg Initiative (CZI) today announced that a joint BU-NYU team will receive nearly $1.5 million over two years to develop a technology that would streamline the engineering of mammalian cells, potentially leading to improvements in cell therapies and functional genomics studies.
“There’s long been a dream in the synthetic biology community that, rather than making individual gene modifications one by one as we do now, we could instead engineer at the level of entire chromosomes,” says Professor Ahmad (Mo) Khalil (BME), the project’s principal investigator. “If we make a technology that can selectively and efficiently transfer chromosomes between different human cells, then we can realize that dream. This would allow us, for example, to engineer artificial human chromosomes that carry large genetic payloads and efficiently move them into immune cells to make cell therapies more effective against incurable solid tumors.”
Khalil is a leader in the emerging interdisciplinary field of synthetic biology, or the engineering of genetic “circuits,” making it possible to program living cells to perform specified tasks. Potential applications abound in medicine, cell therapy, agriculture, biomanufacturing, and more. Khalil, along with co-PIs Liam Holt and Teresa Davoli of New York University (NYU) and key collaborators Jef Boeke of NYU and BU postdoctoral fellow Michael Raymond, responded to a solicitation from CZI for proposals to scale up synthetic biology, advancing the field toward fulfilling its potential. The team’s proposal, “Efficient Chromosome Shuffling for Synthetic Human Genetics,” was one of eight accepted.
A method of transferring chromosomes between mammalian cells does exist, but it has limitations. “It’s a very inefficient process, and worse than that, it only works for particular donor cells and particular acceptor cells,” says Khalil. “We’re taking a radical approach.” The BU-NYU team is combining different technologies, including a new technology developed by postdoctoral fellow Raymond, to create a new method that they call chromosome transfer genetic circuitry (CTGC). “Based on our preliminary data, we have good reason to believe we’ll do much better” in terms of efficiency and programmability.
The work carries implications not only for creating engineered cells and therapies, but also improving how researchers study genetics. “This method would allow us to test how chromosomal variation affects phenotypes, such as drug resistance, in cells. Or one day even mix and match chromosomes from pools of human donor cells to create large-scale genetic variation,” Khalil says.
Synthetic biology holds great promise, but it’s hampered by key bottlenecks in the lab, particularly when it comes to complex mammalian cells. “There’s a need for out-of-the-box thinking and technology development to make genome engineering in relevant human cell types a more scalable, reliable process,” says Khalil. “So I’m thankful that the Chan Zuckerberg Initiative is taking a chance on our being able to combine our ideas, because this could be a real step change.”