Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

Early Humans Took A Giant Evolutionary Leap When They Started Eating Meat

We didn't just grow taller for no reason. Our ancestors didn't just burn energy from meat out of nowhere. Something shifted, deep in our biology – and meat had everything to do with that energy.

A new study published in the journal Cell Genomics dives into this change. It shows how a single genetic tweak, one ancient variant, may have helped drive two things we now take for granted: our height and how much energy our bodies use when at rest.

You might not expect metabolism and height to share roots, but they do. And the story starts with meat.

"The dietary shift from a primarily plant-based diet to increased meat consumption marks a major milestone in human evolution," noted co-corresponding authors Jin Li and He Huang of Fudan University.

"Previous studies have suggested that this shift influenced many traits and phenotypes in anatomically modern humans. It is therefore not surprising that height may also have been affected."

Meat did more than change dinner. It may have changed DNA. Specifically, a variant called rs34590044-A, which affects a gene named ACSF3.

This gene lives in our cells' energy factories – the mitochondria – and helps manage how we break down amino acids, especially those found in meat. When ACSF3 expression goes up, so does metabolism. Bones also seem to grow more.

The researchers didn't guess. They had data from nearly half a million people. They dug into the UK Biobank and found over 6,000 genetic variants that connect height and basal metabolic rate. But one kept flashing bright red: rs34590044-A.

Meat-based diets altered human height

The team ran tests on computer models and in real cells and living mice. When mice got the ACSF3 variant and ate a meat-mimicking diet, they grew longer and used more energy. That's not a fluke – it's a functional effect. The gene works harder when meat is around.

Without the variant, metabolism slowed. Bones didn't grow as much. Mice burned less energy. But once scientists dialed ACSF3 expression back up, everything changed – again. This time, growth returned. So did energy use. But only with the right amino acids in the diet.

"In anatomically modern humans, basal metabolic rate and stature exhibit notable evolutionary divergence compared to non-human apes," said Shaohua Fan of Fudan University in Shanghai, China.

"Although both traits, particularly height, have been extensively investigated, the evolutionary mechanisms driving these changes remain comparatively underexplored. That's why we decided to focus on these two traits together."

Meat gene spread with human migration

It wasn't just today's bodies that told the story. Ancient DNA backed it up. The researchers traced the variant through time. They found it often in meat-eating cultures, like the Yamnaya, and rarely in early plant-farming groups.

The gene didn't spread randomly – it rode the wave of meat consumption across continents and centuries. As farming spread, the variant dipped in frequency. Then, over the past 5,000 years, it came back even stronger.

Populations that reintroduced meat or mixed with meat-eaters showed higher levels again. Evolution doesn't forget what works.

This mutation isn't loud. It doesn't code for muscle or bone directly. It tweaks regulation – how much of ACSF3 gets made. That's enough to tilt the body's internal balance: more ACSF3, more energy, more bone.

A new look at human evolution

ACSF3 doesn't act alone. It reduces toxic byproducts like methylmalonic acid (MMA). That's important because MMA buildup messes with mitochondria. If your cells can't breathe, they can't grow or fuel the body properly. The gene, in a way, cleans the engine before it revs.

When they took ACSF3 out in mice, those animals struggled. Their energy dropped and their bones stopped stretching. But put it back – and give them threonine, an amino acid from meat – and everything reversed. Growth and heat returned.

"This research reveals the intricate interplay between the genetic, environmental, and demographic factors that have contributed to the emergence and evolution of anatomically modern humans," noted Fan.

"It also has important implications for understanding susceptibility and resistance in contemporary metabolic disorders like type 2 diabetes, obesity, and metabolic syndrome."

More energy and warm bodies

This isn't the first time diet shaped us with energy from meat. Our ability to digest milk, for example, only emerged in some farming groups. Starch-digesting genes exploded in others. ACSF3 joins that list –

The gene didn't just help us survive meat – it let us thrive on it. More energy meant better movement, warmer bodies, and longer limbs.

That matters when the world turns cold or when food gets scarce. A fast-burning engine beats a sluggish one when every calorie counts.

Dietary changes in modern humans

The research team plans to keep going. They want to find more traits that co-evolved, just like height and metabolism. They'll keep digging into ancient genomes, testing in labs, and matching genes to diets.

The researchers are especially interested in how our bodies maintain balance. Metabolic homeostasis, the fancy term for it, may have shaped more traits than we realize.

And as diets continue to change today, our ancient genetic choices could still be nudging us in new directions.

The study is published in the journal Cell Genomics.

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Biological Mechanisms Shared Across Psychiatric Disorders

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Researchers at the Max Planck Institute of Psychiatry (MPI), Helmholtz Munich and the University of Sydney identified biological mechanisms that are shared across psychiatric disorders. To do so, the team analyzed postmortem brain tissue samples from the dorsolateral prefrontal cortex (DLPFC). The DLPFC is the center for reasoning and emotions in the brain, and is often implicated in psychiatric disorders. Samples from affected individuals, most of whom were schizophrenia patients, and healthy controls were included in the study.

What makes this study special: The research team combined several different layers of genetic data. "In contrast to studies that look at gene expression as a whole, we analyzed the exon level to better understand the structure of the genes. This detailed approach gave us a better understanding of how genetic variation influences disease risk", first author Karolina Worf explains.

Exons are the essential, information-containing segments of a gene. In addition to providing the blueprint for building proteins, they also determine which versions of a protein ultimately arise from a gene. This happens through alternative splicing, a process that occurs in over 95 percent of human genes.

Including the exon level in the analysis was an important step: While samples from psychiatric patients and healthy controls were not significantly different at the gene level, they were significantly different at the exon level. "The risk of developing a psychiatric disorder seems to therefore not just depend on what genes you have, but how your genes are expressed", Janine Knauer-Arloth, leader of the Project Group Medical Genomics at the MPI, explains.

The team integrated different genetic data, including variations in individual base pairs of DNA (single nucleotide polymorphisms, or SNPs), rare genetic variants and polygenic risk scores, which summarize a person's disease risk by aggregating all relevant genetic variants. This way, the researchers discovered disruptions in pathways related to the circadian rhythm, the release of the stress hormone cortisol, and the neurotransmitter dopamine — across all three included disorders.

These results show that psychiatric disorders share a common biological basis. In the long-term, this knowledge can help researchers to classify psychiatric disorders not only based on symptoms, but also based on biological mechanisms. This paradigm shift is significant a step towards more precise diagnoses and treatment.

Reference: Worf K, Matosin N, Gerstner N, et al. Exon-variant interplay and multi-modal evidence identify endocrine dysregulation in severe psychiatric disorders impacting excitatory neurons. Transl Psychiatry. 2025;15(1):1-13. Doi:10.1038/s41398-025-03366-8

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Efficient Gene Insertion In Human Cells

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evoCAST uses a CRISPR complex and transposase enzyme to insert whole genes into human DNA at targeted locations.

David Liu and Richard Merkin of the Broad Institute of MIT and Harvard, along with Columbia professor Sam Sternberg, have developed a new, targeted means of inserting entire genes into human DNA (Science 2025, DOI: 10.1126/science.Adt5199).

The new tool is called evoCAST, so named because it was created using a Liu-developed evolution technique on CRISPR-associated transposases (CASTs). CRISPR enables the targeting of precise sequences of DNA via a guide RNA—famously a core component of the CRISPR-Cas systems of gene editors. Transposases are enzymes that that cut and paste DNA within a genome; they're the active component of some transposons, also known as jumping genes, which are so prolific that they make up roughly 50% of the human genome.

Shondra Pruett-Miller, a genome engineer at St. Jude's Children's Research Hospital who was not involved in the research, says that evoCAST is "a huge step forward" and that scientists have been working to create a CAST that can efficiently engineer human cells for about a decade.

CAST systems aren't found in humans, and when used in human cell cultures they produce a successful DNA insertion only 0.1% of the time—far too low for gene therapy purposes. But after conducting hundreds of rounds of directed evolution, the team crafted a CAST that could make a successful insertion 10–20% of the time, which Pruett-Miller says could be efficient enough to be therapeutically useful for some diseases.

Other technologies for whole gene insertion exist, including other CAST- and transposase-based technologies. But many are limited in that they can inadvertently create mutations at the target site or can't target specific insertion regions at all, according to Pruett-Miller.

The efficiency of evoCAST gives it a competitive advantage, though Pruett-Miller acknowledges there's room for improvement: "I think this technology still needs a bit of refinement in order to make it to the clinic. The delivery is going to be a major issue." The evoCAST system relies on a complex of proteins and a guide RNA, all of which can be hard to package and to deliver to specific cells—a common problem in many gene therapies.

The gene-editing field is still a developing space. The news of evoCAST's development comes as Prime Medicine—cofounded by Liu to commercialize a different technology, Prime Editing—announced the successful demonstration of one of its therapies, PM359, in a patient with chronic granulomatous disease. But the same day, Prime changed CEOs, laid off a quarter of its staff, and stopped work on PM359 to focus on other areas of research.

UPDATE

This story was updated on May 22, 2025, to clarify that Shondra Pruett-Miller was not involved with the development of evoCAST.

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