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The Gene Editing Revolution: David Liu’s Transformative Innovations

A groundbreaking transformation in gene editing is being driven by David Liu, an esteemed molecular biologist whose innovative research is fundamentally changing the landscape of genetic science.

As a professor at the Broad Institute of MIT and Harvard, Liu recently received the prestigious Breakthrough Prize in Life Sciences for developing two significant technologies. One is already enhancing the lives of patients with severe genetic disorders, while the other holds the promise of profoundly impacting medicine in the near future.

In an interview ahead of the award ceremony in Los Angeles, Liu expressed his plans to donate a substantial portion of the $3 million prize to his charitable foundation, emphasizing the importance of innovation in improving healthcare. “The ability to change a DNA sequence of our choosing into a new sequence of our choosing is a fundamentally very powerful capability,” he noted, highlighting potential applications not only in human medicine but also in agriculture, such as creating crops that are more nutritious or resistant to diseases.

Addressing Genetic Errors

DNA comprises four chemical bases—adenine (A), guanine (G), cytosine (C), and thymine (T)—and mutations within this sequence are responsible for numerous human diseases. Historically, gene editing has been able to target only a limited array of these mutations.

While CRISPR-Cas9, a pioneering technique awarded a Nobel Prize in 2020, represented a major advancement, it has its drawbacks. This method cleaves both strands of DNA, making it more effective for disrupting genes rather than correcting them, and can sometimes inadvertently create additional errors.

Liu’s insights led to the creation of base editing, which involves a modified Cas9 protein that can locate a specific DNA sequence without cutting both strands. Rather than disrupting the genetic code, this approach allows for precise conversions of one base into another, such as changing C to T or G to A.

However, reversing edits proved challenging, prompting Liu’s team to engineer new enzymes capable of this task. Now, base editing can rectify around 30% of mutation types responsible for genetic diseases, and this technology is already being explored in over 14 clinical trials. One notable trial involves Beam Therapeutics, a company co-founded by Liu, which reported successful treatment of patients with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disorder.

Hope for Cystic Fibrosis and Beyond

Despite its potential, base editing, often referred to as “CRISPR 2.0,” cannot address every genetic mutation. Approximately 70% of known harmful mutations remain outside its reach, particularly those involving missing or additional base pairs.

To broaden the scope of gene editing, Liu’s lab developed prime editing in 2019. This advanced method can replace entire segments of faulty DNA with accurate sequences. If CRISPR functions like scissors, and base editing like a pencil correcting a word, then prime editing serves as a word processor’s “find and replace” feature, offering a vastly more versatile editing approach.

The creation of prime editing necessitated a series of significant breakthroughs that Liu’s team describes as “small miracles.” Liu highlighted ongoing research targeting diseases such as cystic fibrosis, which is often caused by the absence of three specific DNA letters that lead to severe health complications.

Liu is committed to sharing knowledge and resources; his lab has made many of its findings and DNA blueprints accessible through a nonprofit platform utilized by thousands of laboratories globally. “The science we create—which is ultimately funded by society—should ultimately benefit society,” he stated.

These advancements in gene editing come during a challenging time for the scientific community in the U.S., with significant budget cuts to research institutions like the National Institutes of Health (NIH). Liu expressed concern over this trend, emphasizing the importance of the NIH in supporting science, both nationally and globally. “Trying to dismantle the heart of what supports science in this country is like burning your seed corn,” he asserted.

Source
phys.org