Chirality in biology is much like the difference between your left and right hands—distinct mirror images that can’t be superimposed. This concept, known as molecular chirality, is fundamental to life as we know it. For instance, the DNA in your cells is made up of right-handed chiral molecules, which combine to form the classic right-handed double helix. Its left-handed counterpart, if it existed, would twist in the opposite direction, creating a strikingly different structure.

Nature, however, has a bias—it favors one side. On Earth, DNA and RNA are strictly right-handed. Even when scientists synthesize left-handed versions, these molecules behave like true opposites, unable to interact with their counterparts. But what if that could change? What if we could bridge the gap between left- and right-handed molecules, unlocking a whole new realm of biological possibilities?

That’s precisely what researchers at the Salk Institute have done. In a groundbreaking study published recently in PNAS, scientists have achieved the first cross-chiral exponential amplification of an RNA enzyme. By leveraging advanced bioengineering, they’ve created a system where left- and right-handed RNA enzymes can essentially “reach through the mirror” and replicate each other. This cross-chiral self-replication leads to exponential growth—a hallmark of living systems.

According to NASA, life is defined as "a self-sustaining chemical system capable of Darwinian evolution." What the Salk team has discovered may be the first sign of a life-like system capable of thriving on both sides of chirality’s mirror.

Breaking Boundaries: Engineering Life’s Essential Function

“Exponential self-replication is crucial for growth and evolution in every living system,” explains Gerald Joyce, co-corresponding author and president of Salk. “Living cells don’t just replicate; they multiply exponentially, driving competition, natural selection, and evolution. We’ve now engineered forms of genetic self-replication that, while not yet life, are pushing the boundaries. These systems are built on the interaction of left- and right-handed molecules.”

While such cross-chiral replication is unlikely to occur spontaneously in nature, this breakthrough in the lab suggests that scientists could one day synthesize artificial life that utilizes both left- and right-handed molecules. The potential implications are enormous, from studying a new form of biochemical evolution to creating entirely novel biotechnologies and therapeutics.

David Horning, a senior scientist at Salk and co-corresponding author, is optimistic about the possibilities: “Life as we know it is single-handed, but bioengineers aren’t bound by that rule. We’re pushing the limits of what biology can be, and this study shows that life’s definition doesn’t have to be as narrow in the lab as it is in nature.”

A Parallel Biology: Beyond Nature’s Limits

To achieve this cross-chiral exponential amplification, co-first authors Wesley Cochrane and Grant Bare expanded upon methods for driving the directed evolution of RNAs. They created an RNA enzyme capable of making the opposite-handed version of itself with incredible efficiency. This discovery opens the door to a new realm of biochemistry, where engineered systems could produce RNA molecules with functions that don’t naturally exist.

One potential application is the development of cross-chiral therapeutics—drugs composed of left-handed RNA that interact with the body’s right-handed molecules in precise ways. Because these left-handed molecules would be virtually invisible to the immune system and wouldn’t degrade as quickly as traditional drugs, they could offer longer-lasting, more targeted treatments with fewer side effects. These therapies could revolutionize medicine, allowing for the design of drugs that interact only with specific disease-related targets, leaving healthy cells unharmed.

In fact, Joyce’s lab is already working on left-handed RNAs that bind to proteins and RNAs associated with diseases. They’re also exploring ways to use these mirrored molecules as signal amplifiers, making it easier to detect trace amounts of specific molecules, such as viral RNA, in diagnostic tests.

“It’s like having a parallel biology,” says Horning. “This biology exists alongside ours, but it’s completely designed by us. Nature can’t interfere with it. Cross-chiral self-replication offers a whole new world of biochemical possibilities, and we’re only beginning to explore the ways we can use these mirrored molecules for our benefit.”