A DNA hack could one day save us from future heart attacks

First cue

When we admire a creature like a lizard, a starfish or a worm that can regenerate body parts after injury, we really marvel at two qualities: the ability of these animals to regrow and to stop regrowing. Because in fact, a high degree of genetic precision is needed to reduce the growth signals that, when left unchecked, are a hallmark of cancer.

Scientists are obsessed with this tightrope of regulated growth to one day help humans recover from heart attacks and other life-threatening injuries. Now, a new study led by biologists at Duke University and published Tuesday in the journal Cell Stem Cell brings us closer to understanding regeneration by copying and pasting fish DNA into mouse and pig hearts.

Pig heart transplants for humans are already working better than doctors hoped

The genetic code of living organisms is made up of genes – regions that code for proteins – and a vast collection of DNA that provides no instructions for making anything. Instead, so-called non-coding regions can modulate and alter protein outputs from genes. In zebrafish (a small minnow often studied by scientists as a model organism), regeneration depends on activators, which are a type of non-coding genetic element. Zebrafish-specific activators activate, activate, and then decrease regrowth when injured, and the researchers wondered if these activators would have the same effect in other organisms.

Duke’s team modified the genetic code of mice and pigs to introduce these zebrafish enhancers, then created injuries by amputating digits, fracturing bones or injecting a toxic compound into their skeletal muscle. When injected before the time of injury or slightly after, zebrafish enhancers go to work, changing the types and amount of protein the animals make.

Harvard scientists have invented a ‘biohybrid’ fish with a human heart

In a later experiment to discern how enhancers affected cell repair, the researchers modified a tissue growth gene and tracked how, after a mouse had a heart attack, an enhancer activated the growth gene and then the reduced after several weeks.

There’s a lot researchers still don’t know about activators – how many genes they affect and what kind of regeneration they can and can’t promote – but they might be more prevalent than previously thought, even in creatures who cannot regrow limbs. Like the end of a feel-good adventure movie, researchers believe that mice and other mammals like humans may have had this activating DNA in our systems all along.

“Mammals probably possess all the genetic products needed to regenerate an injured heart, crushed spinal cord connections, or amputated limbs,” the researchers wrote in the study. The trick, it seems, will be to learn how to activate these elements.

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