Scientists Discover Simple Amino Acid Cocktail That Boosts mRNA and CRISPR Delivery

A team of scientists at Biohub has found that co-injecting three common amino acids alongside lipid nanoparticles — the same delivery technology behind COVID-19 mRNA vaccines — can increase mRNA delivery to cells up to 20-fold and push CRISPR gene editing efficiency from roughly 25% to nearly 90% in a single dose, according to a study published Wednesday in Science Translational Medicine.

The discovery, led by Daniel Zongjie Wang and Shana O. Kelley, offers a strikingly simple workaround to one of the most persistent obstacles in genetic medicine: lipid nanoparticles, or LNPs, work far better in laboratory dishes than they do inside living organisms.

A Metabolic Bottleneck, Not a Design Flaw

Rather than attempting to engineer a better nanoparticle, the Biohub team investigated why cells in the body are so much worse at absorbing LNPs than cells grown in standard lab conditions. They found that when cells were cultured in a medium mimicking the nutrient-lean environment of human blood plasma, LNP uptake dropped 50% to 80%.

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Metabolic analysis traced the problem to suppressed amino acid pathways. "The field has spent enormous effort engineering nanoparticles," Wang said. "We found, however, that the cell's own metabolic state is an equally important — and addressable — part of the equation."

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Through systematic screening, the team identified an optimized supplement of methionine, arginine, and serine that restored and amplified the cellular uptake pathway. The cocktail worked across intramuscular, intratracheal, and intravenous delivery routes and was effective regardless of the specific lipid formulation or mRNA cargo used.

Striking Results in Preclinical Models:

In mice with acetaminophen-induced acute liver failure, LNPs carrying growth hormone mRNA produced only a 33% survival rate when administered alone. With the amino acid supplement, every mouse survived, therapeutic protein levels rose nearly nine-fold, and markers of liver damage dropped to near-healthy levels.

In a separate set of experiments targeting lung tissue with CRISPR-Cas9, a single dose without the supplement achieved editing efficiencies of 20% to 30%. Adding the amino acid cocktail pushed that figure to 85% to 90% — a result that could prove transformative for diseases like cystic fibrosis that demand efficient gene correction in the lungs.

JWST detects dry ice in a planetary nebula for the first time

Astronomers have discovered carbon dioxide ice — commonly known as dry ice — inside a planetary nebula for the first time, using the James Webb Space Telescope to peer into the heart of NGC 6302, the Butterfly Nebula.

The finding, detailed in a paper published February 25 on the arXiv preprint server, challenges the assumption that planetary nebulae are too hostile for fragile molecular ices to survive. The research was led by Charmi Bhatt of the University of Western Ontario in Canada and involved an international team of 26 scientists from institutions across North America, Europe, and South America.

A Surprising Detection

NGC 6302, also called the Bug Nebula, is a bipolar planetary nebula located roughly 3,400 light-years from Earth in the constellation Scorpius. At its center lies the ancient core of a Sun-like star, surrounded by a massive dusty torus and bright lobes of expelled gas.

Using JWST's Mid-Infrared Instrument (MIRI), the team identified two absorption features characteristic of pure, crystalline carbon dioxide ice within the nebula's dusty torus. The ice absorption profile displayed a distinctive double-peak pattern between 14.9 and 15.3 micrometers, accompanied by cold gas-phase carbon dioxide at temperatures of 20 to 50 Kelvin along the same lines of sight.

Planetary nebulae are expanding shells of gas and dust shed by dying stars, and their environments are generally bathed in intense ultraviolet radiation — conditions long thought to destroy delicate ice molecules. The detection suggests the dense torus around NGC 6302's central star provides enough shielding for ice chemistry to persist.

Distinct Chemistry in a Dying Star's Envelope

The researchers found that the ratio of gas-phase to ice-phase carbon dioxide in NGC 6302 is more than an order of magnitude higher than what is typically observed in young stellar objects, according to the paper. This points to a fundamentally different ice formation or processing mechanism in evolved stellar environments compared to the cold molecular clouds and protoplanetary disks where ices are more commonly found.

The result builds on earlier JWST observations of NGC 6302 that revealed the presence of methyl cation and polycyclic aromatic hydrocarbons, suggesting the nebula hosts unexpectedly rich organic chemistry. The authors emphasized that future high-resolution observations of planetary nebulae will be essential to determine whether ice chemistry is common in dense nebular tori, or whether the Butterfly Nebula is an outlier.