Targeting Allele-Specific Faulty MRNA In SCNA2 Mutation Patients

July 23, 2026 by Maya Posch 1 Comment

When an individual is born with genetic defects, there are a few ways to deal with the impact of the faulty genes. The most extreme solution is direct DNA editing to repair the mutation, while the treatment of symptoms with medication is the least invasive, though this comes with its own set of disadvantages. Antisense therapy keeps a middle ground here, by targeting the messenger RNA (mRNA) that forms the bridge between DNA and the translation into a functional protein by the ribosome.

In a recent study by [Olivia Kim-McManus] et al. antisense therapy with an allele-specific feature was demonstrated in two individuals with SCN2A mutations. These mutations had resulted in severe epilepsy and developmental disorders, due to how instrumental this gene is for normal functioning of the human central nervous system (CNS) where it regulates the initiation of action potentials.

Although SCN2A mutations are rarely inherited, for the approximately 1 in 80,000 affected the consequences can be quite dramatic. The two major types of mutations are classified as gain-of-function (GoF) and loss-of-function (LoF) with respectively hyper- and hyposensitivity of the resulting NA_v1.2 sodium channels.

This translates especially in the case of GoF mutations into various symptoms, ranging from mild to severe (daily) epileptic attacks starting as an infant, stalled neurodevelopment and various types of autism (ASD). Often sodium channel blockers are prescribed for the GoF cases to limit epileptic attacks.

Usually with the responsible mutations only a single copy of the gene is affected, so while regular antisense therapy could be used, this would risk also modifying the healthy SCN2A mRNA copy. To get around this, an individualized treatment was developed, targeting the allele with the mutated gene for the two patients in the study: 9- and 14-year old boys with severe developmental and epileptic encephalopathies (DEE) that had left them with daily seizures and despite sodium-channel blockers and other typical medications.

Study outcome of the 14-year old boy with DEE after ASO therapy. (Credit: Kim-McManus et al., Nature Medicine, 2026)

During the trial, the 9-year old boy received 12 doses over 24 months of antisense oligonucleotides (ASOs) adapted to his affected allele, allowing for the cessation of the anti-seizure medication phenytoin, with an overall reduction in seizures. In the case of the 14-year old boy 8 doses were administered over 16 months, resulting in an average of two seizures a day being reduced to zero.

Although the focus of the study was on treating these seizures, by addressing the underlying cause of faulty mRNA transcriptions, changes in the neurodevelopmental state could also be observed. In particular language and motor skills improved, with erratic and irritable behavior reducing. The by then 15-year year old boy was able to walk unassisted, showing clear progression from the previous infantile state.

The advantage of ASOs over typical anti-seizure medication is of course that it directly addresses the faulty mRNA and thus the resulting faulty sodium channels. Since ASOs tend to hang around in a cell for a considerable amount of time, they could be quite a viable alternative treatment even for less severe cases. Whether early application of individualized ASOs in affected infants could lead to a more or less normal neurodevelopment would also be an interesting study question.

Naturally, directly addressing the faulty gene or upregulating the healthy gene would be the ideal and permanent solution, with research here also underway in mice models with the use of CRISPR-based tools.

Better Beer Through Gene Editing

March 27, 2018 by Kristina Panos 63 Comments

As much as today’s American beer drinker seems to like hoppy IPAs and other pale ales, it’s a shame that hops are so expensive to produce and transport. Did you know that it can take 50 pints of water to grow enough hops to produce one pint of craft beer? While hops aren’t critical to beer brewing, they do add essential oils and aromas that turn otherwise flat-tasting beer into delicious suds.

Using UC Berkley’s own simple and affordable CRISPR-CaS9 gene editing system, researchers [Charles Denby] and [Rachel Li] have edited strains of brewer’s yeast to make it taste like hops. These modified strains both ferment the beer and provide the hoppy flavor notes that beer drinkers crave. The notes come from mint and basil genes, which the researchers spliced in to yeast genes along with the CaS9 protein and promoters that help make the edit successful. It was especially challenging because brewer’s yeast has four sets of chromosomes, so they had to do everything four times. Otherwise, the yeast might reject the donor genes.

So, how does it taste? A group of employees from a nearby brewery participated in a blind taste test and agreed that the genetically modified beer tasted even hoppier than the control beer. That’s something to raise a glass to. Call and cab and drive across the break for a quick video.

Have you always wanted to brew your own beer, but don’t know where to start? If you have a sous vide cooker, you’re in luck.

Continue reading “Better Beer Through Gene Editing” →

Living Logic: Biological Circuits For The Electrically Minded

August 21, 2017 by Michael Uttmark 18 Comments

Did you know you can build fundamental circuits using biological methods? These aren’t your average circuits, but they work just like common electrical components. We talk alot about normal silicon and copper circuits ‘roud here, but it’s time to get our hands wet and see what we can do with the power of life!

In 1703, Gottfried Wilhelm Leibniz published his Explication de l’Arithmétique Binaire (translated). Inspired by the I Ching, an ancient Chinese classic, Leibniz established that the principles of arithmetic and logic could be combined and represented by just 1s and 0s. Two hundred years later in 1907, Lee De Forest’s “Audion” is used as an AND gate. Forty years later in 1947, Brattain and H. R. Moore demonstrate their “PNP point-contact germanium transistor” in Bell Labs (often given as the birth date of the transistor). Six years later in 1953, the world’s first transistor computer was created by the University of Manchester. Today, 13,086,801,423,016,741,282,500¹ transistors have built a world of progressing connectivity, automation and analysis.

While we will never know how Fu Hsi, Leibniz, Forest or Moore felt as they lay the foundation of the digital world we know today, we’re not completely out of luck: we’re in the midst’s of our own growing revolution, but this one’s centered around biotechnology. In 1961, Jacob and Monod discovered the lac system: a biological analog to the PNP transistor presented in Bell Labs fourteen years earlier. In 2000, Gardner, Cantor, and Collins created a genetic toggle switch controlled by heat and a synthetic fluid bio-analog². Today, AND, OR, NOR, NAND, and XOR gates (among others) have been successfully demonstrated in academic labs around the world.

But wait a moment. Revolution you say? Electrical transistors went from invention to computers in 6 years, and biological transistors went from invention to toggle button in 40? I’m going to get to the challenges facing biological circuits in time, but suffice it to say that working with living things that want to be fed and (seem to) like to die comes with its own set of challenges that aren’t relevant when working with inanimate and uncaring transistors. But, in the spirit of hacking, let’s dive right in. Continue reading “Living Logic: Biological Circuits For The Electrically Minded” →

How Biohackers Are Fighting A Two-front War On Antibiotic Resistance

September 8, 2015 by Dan Maloney 39 Comments

We humans like to think of ourselves as the pinnacle of evolution on the planet, but that’s just a conceit. It takes humans roughly twenty years to reproduce, whereas some bacteria can make copies of themselves every 20 minutes. Countless generations of bacteria have honed and perfected their genomes into extremely evolved biological machines.

Most bacteria are harmless, and some are quite useful, even tasty – witness the lactofermented pickles and sauerkraut I made this summer. But some bacteria are pathogenic nightmares that have swarmed over the planet and caused untold misery and billions of deaths. For most of human history it has been so – the bugs were winning. Then a bright period dawned in the early 20th century – the Era of Antibiotics. At last we were delivered from the threat of pestilence, never more to suffer from plague and disease like our unfortunate ancestors. Infections were miraculously cured with a simple injection or pill, childhood diseases were no longer reaping their tragic harvest, and soldiers on the battlefield were surviving wounds that would have festered and led to a slow, painful death.

Now it seems like this bright spot of relief from bacterial disease might be drawing to an end. Resistant strains of bacteria are in the news these days, and the rise of superbugs seems inevitable. But is it? Have we run out of tools to fight back? Not quite yet as it turns out. But there’s a lot of work to do to make sure we win this battle.

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