Scientists have figured out how to take gene editing to a whole new level, making extremely precise changes that may one day allow us to prevent the onset of some genetic diseases.
The study, published this week in the journal Nature, describes the highly complex method by which researchers created what’s essentially a molecular machine—a so-called base editor—that can go into targeted cells and perform incredibly precise surgery on DNA. In doing so, the researchers say they are one step closer to using gene editing to potentially solve a host of illnesses.
Human DNA is made up of four nucleobases: adenine (A), cytosine (C), guanine (G), and thymine (T), which are the fundamental units of genetic coding. Those nucleobases naturally pair off in a typical DNA double-helix—and sometimes mutate, which can lead to thousands of disorders. One way scientists are trying to fix those mutations is through high-tech editing technology.
A lot of fine-tuned genetic tinkering in recent years has been performed with CRISPR-Cas9 technology, a genome-editing tool that facilitates snipping, adding, or changing parts of a DNA sequence. It makes double-stranded breaks in the sequencing, which is useful when trying to delete a mutation. That process has been likened to using a pair of scissors on our DNA. By contrast, the new base editor described in the Nature article was likened to a pencil—allowing scientists to make extremely precise alterations to an individual nucleobase.
As laid out by Harvard University researcher David Liu, the study looked into cases where adenine pairs with thymine (A, T) and guanine with cytosine (G, C). By far, the most common kinds of diseases related to genetic mutations in human occur when a “GC” pairing mutates into an “AT” pairing. It makes up about half the mutations that affect humans.
With that in mind, Liu and his team set out to find a way to trick cells into turning an “AT” base pair into a “GC” pair.
They were successful, a scientific breakthrough that could represent a major step toward eliminating the types of mutations that can wreak havoc on the body.
One example Liu used was a theoretical process by which scientists might one day combat conditions such as adult sickle-cell anemia, which is caused by defects in adult hemoglobin genes. In addition to those adult genes, humans also all have fetal hemoglobin genes that naturally fix the defects in the adult genes. But our bodies often silence those fetal genes as we get older. Using new gene-editing technology, Liu said it’s possible to wake them up and allow them to work against the defects that could lead to sickle cell.
“A tremendous amount of work is still needed before these machines can be used to treat molecular diseases in humans,” Liu says, adding that the new tool will hopefully allow open more doors for geneticists to experiment. “We hope these tools will be widely used in the community.”