BEIJING, China — A single injection of an experimental gene-silencing drug cut a key blood-pressure protein by up to 93% in healthy volunteers, according to results from a small first-in-human trial published in JAMA Cardiology and reported on 31 October 2026. The drug, called ART101, is designed to work for months from one shot — a striking contrast to the daily tablets most people with high blood pressure must take for life.
The findings are early, and the researchers are careful about what they do and do not prove. The trial was built to test safety, not to show that the drug treats hypertension. But the size and durability of the protein drop, sustained over 24 weeks of follow-up, give researchers a dose range to carry into larger trials in patients — the next step that will decide whether the idea becomes a real treatment.
Illustration: A clinician giving a single subcutaneous injection, the dosing approach tested in the ART101 Phase 1 trial.
What Happened
The Phase 1 study was conducted at Beijing Friendship Hospital, part of Capital Medical University, from January 2025 to April 2026, with each participant followed for 24 weeks after dosing. It had two parts. In part A, 40 healthy adults were randomised, six to two, to receive a single subcutaneous injection of ART101 or a matching placebo, across five ascending doses: 25, 75, 150, 300 and 600 milligrams. Thirty participants received the active drug and 10 received placebo; 39 of the 40 completed the study.
In part B, eight patients with hypertension received a single open-label 600-milligram injection. All eight completed the study. That group was exploratory by design: with no comparison group and only eight people, it can offer safety information and early signals, but it was not powered to prove that the drug lowers blood pressure in patients.
The headline result concerns angiotensinogen, known as AGT — a protein made mainly by the liver that sits at the very top of the body's blood-pressure-raising chain. At the highest dose, the average maximum reduction in blood AGT was 93% in healthy volunteers and 90% in the patients with hypertension. The reduction grew with dose, and it lasted: at 24 weeks after a single 600-milligram dose, healthy participants showed a placebo-corrected fall of 12.9 mm Hg in 24-hour ambulatory systolic blood pressure, an exploratory measure that the authors present as hypothesis-generating rather than proof of treatment benefit.
On safety, the drug was well tolerated in this small, early test. Treatment-emergent adverse events occurred in 76.7% of participants on the active drug and 70.0% of those on placebo in part A, and in 75.0% of the patients in part B. All reported events were mild to moderate. The study reports no serious adverse events, no injection-site reactions and no dangerous rise in blood potassium, a complication doctors watch for with drugs that interfere with this hormone system.
Background
To understand why researchers are excited — and why they urge caution — it helps to follow the chain ART101 interrupts. Angiotensinogen is the raw material for angiotensin, a hormone that tightens blood vessels and tells the kidneys to hold on to salt and water. Most widely used blood-pressure medicines act further down this chain: ACE inhibitors and angiotensin receptor blockers, for example, block steps that come after angiotensinogen is made. Those drugs work, but blocking the chain downstream can trigger compensatory mechanisms that limit their effect.
ART101 goes to the source. It is a small interfering RNA, or siRNA — a short strand of genetic material designed to find the liver cells' instructions for making angiotensinogen and have them destroyed. A sugar tag called N-acetylgalactosamine, or GalNAc, guides the molecule almost exclusively into liver cells, which is where most circulating angiotensinogen is produced. Because the silencing effect persists inside those cells, a single injection under the skin can keep the protein low for weeks to months, in the same broad family as twice-yearly cholesterol-lowering RNA injections already in use.
Illustration: The liver, where most angiotensinogen is made, and the RNA-silencing approach ART101 uses to reduce it at its source.
The problem ART101 hopes to address is large and stubborn. Hypertension remains the leading modifiable risk factor for cardiovascular disease, affecting an estimated 1.3 billion adults worldwide, according to the study's introduction, and raising the risk of stroke, heart failure, kidney impairment and death. Despite effective medicines, treatment and control rates remain suboptimal, largely because many people struggle to take daily tablets for years on end. A treatment that needs to be given only a few times a year — if it proves safe and effective — could change that arithmetic, which is why long-acting approaches are an active area of research.
Before this human trial, the approach had been tested in laboratory and animal models expressing human angiotensinogen, where a single dose reduced the protein by 90% within a week in mice, with the effect slowly returning toward baseline over seven weeks, and in toxicology studies in rats and monkeys that supported moving into people. The new trial is the first to test the drug in humans.
Why It Matters
The most important result is not a blood-pressure number — it is a safety and dosing foundation. First-in-human trials exist to answer a narrow question: can this drug be given to people without unacceptable harm, and at what dose does it do what it is designed to do? On both counts, the ART101 trial gives encouraging answers. No serious safety signal emerged, the protein fell in a dose-dependent way, and the effect was still visible at six months. That is what allows researchers to pick doses for the larger trials that must follow.
The blood-pressure signal, while eye-catching, needs to be read with the authors' own caveats attached. The 12.9 mm Hg fall was measured in healthy volunteers, not in patients being treated for hypertension, and it was an exploratory outcome in a trial with no formal hypothesis testing — the analyses were descriptive throughout. In the eight patients with hypertension, blood-pressure changes were also exploratory, and the study itself states that this part was not powered to assess antihypertensive efficacy. A fall in a protein, however large, is not the same as a proven treatment, and the trial was not designed to show fewer strokes or heart attacks.
The study's limits also matter for how widely the results apply. The participants were few — 48 people in total — and mostly Han Chinese, with a mean age of about 40 in the healthy group and 47 in the patient group. People with poorly controlled diabetes, significant kidney impairment and several other conditions were excluded. Follow-up lasted 24 weeks, so the trial says nothing yet about safety or benefit over years, which is the timescale on which a hypertension treatment would actually be used. The authors conclude only that the findings support further investigation of the drug as a potential long-acting therapy.
For patients, the practical message today is unchanged: ART101 is investigational, it is not available as a treatment, and no one should stop or change a prescribed blood-pressure medicine because of an early trial result. Anyone interested in future trials should discuss options with their own clinician.
Illustration: Blood-pressure monitoring over months, the kind of long follow-up larger trials will need before any long-acting treatment can be judged.
What Happens Next
The next steps are larger, longer trials in people who actually have hypertension. Those studies will need to test whether the protein reduction translates into reliable, sustained blood-pressure control, what dosing interval makes sense, and whether the safety profile holds in more diverse populations and in people with other health conditions. Researchers will also be watching potassium levels, kidney function and blood-pressure variability closely, since interfering with the renin-angiotensin system requires care.
Regulators will want evidence from randomised, controlled trials with enough participants and long enough follow-up to judge both benefit and harm — a process that takes years even when early results are promising. If ART101 or a similar drug eventually succeeds, it would join a small but growing class of long-acting RNA therapies aimed at chronic conditions where daily tablets fail many patients. If it does not, the trial will still have mapped the dose range and safety boundaries for the next candidate. Either way, the 93% figure is a starting point for that work, not its conclusion.
Health information note: This article reports on published research and is for general information only. It is not medical advice, and it does not replace guidance from a qualified health professional.
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FAQ
What is ART101?
ART101 is an investigational GalNAc-conjugated small interfering RNA designed to durably suppress the liver's production of angiotensinogen, the protein at the top of the body's blood-pressure-raising hormone chain. It is not an approved treatment.
What did the Phase 1 trial actually test?
Primarily safety and tolerability. Forty healthy adults received a single injection of ART101 at doses from 25 to 600 milligrams or a placebo, and eight patients with hypertension received a single 600-milligram dose, with 24 weeks of follow-up.
How large was the effect?
At the highest dose, average maximum blood angiotensinogen fell by 93% in healthy volunteers and 90% in patients with hypertension. Healthy participants also showed an exploratory, placebo-corrected 24-hour systolic blood-pressure fall of 12.9 mm Hg at 24 weeks — a signal that needs confirmation in larger trials, not proof of treatment benefit.
Was the drug safe in this early trial?
It was well tolerated in this small study: all reported adverse events were mild to moderate, at similar rates in the drug and placebo groups, with no serious adverse events, no injection-site reactions and no hyperkalemia reported. Small, short trials cannot rule out rarer or longer-term risks.
Can people with high blood pressure get ART101 now?
No. ART101 remains investigational and is available only in research settings. People with hypertension should continue their prescribed treatment and speak to their clinician about any questions raised by early trial reports.
Sources
- Zhang, J., et al., "N-Acetylgalactosamine–Conjugated Small Interfering RNA Targeting Hepatic Angiotensinogen in Hypertension: A Phase I Clinical Trial With Randomized Part A and Open-Label Part B," JAMA Cardiology (2026), Beijing Friendship Hospital, Capital Medical University; trial registrations CTR20250041 (part A) and CTR20253973 (part B).
- CiVL, "A single shot that quiets a blood pressure protein for months in healthy volunteers," published 31 October 2026, summarising the JAMA Cardiology Phase 1 results.
- JAMA Cardiology study introduction, on hypertension affecting an estimated 1.3 billion adults worldwide and on the limitations of daily oral regimens and downstream renin-angiotensin blockade.
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