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Nucleic acid drugs

siRNA, ASO, mRNA therapeutics and vaccines: delivery, indication expansion and safety.

80 picksRelatedGene therapy & editingRare diseaseCardiometabolic

Latest picks

41–60 of 80
Sep 6Sun
  1. WeChat73

    Pelacarsen Lowered Lp(a) but Failed to Cut Cardiovascular Risk in Pivotal Trial

    Pelacarsen, Novartis's antisense drug targeting Lp(a), significantly lowered Lp(a) but failed to translate that into reduced cardiovascular risk in a pivotal trial, the first to test whether lowering Lp(a) cuts cardiovascular risk. Novartis shares fell 5% after the news and Ionis fell 9%. The result clouds the most closely watched lipid target after PCSK9, where several small nucleic acid drugs and small molecules are in late-stage trials.

    Why it matters: First pivotal test of Lp(a) lowering for cardiovascular benefit failed despite effective Lp(a) reduction.

  2. WeChat68

    Novartis pelacarsen fails to improve cardiovascular events in Lp(a)HORIZON phase III trial

    Novartis reported topline results from the Lp(a)HORIZON phase III trial of pelacarsen, an Lp(a)-targeting oligonucleotide therapy, in patients with elevated Lp(a) and established cardiovascular disease. Pelacarsen did not improve cardiovascular events compared with placebo. The result adds new evidence on the relationship between Lp(a) lowering and cardiovascular outcomes.

    Why it matters: Phase III failure of a leading Lp(a)-lowering therapy directly tests the Lp(a) cardiovascular hypothesis.

Sep 5Sat
  1. STAT65

    STAT+: Novartis’ experimental cardiovascular drug fails a pivotal study

    Novartis' pelacarsen failed to reduce the risk of cardiovascular death or emergencies such as heart attack or stroke compared with placebo in the Phase 3 HORIZON trial, despite earlier trials showing it drastically lowered Lp(a), a lipid-and-protein particle linked to severe heart problems. The outcome is a setback for Novartis and for the broader effort to target Lp(a), where Amgen and Eli Lilly are also developing therapies.

    Why it matters: Pivotal failure of a leading Lp(a)-lowering candidate reshapes a cardiovascular pipeline race involving Amgen and Eli Lilly.

  2. 顶刊论文（社媒热度）61

    Inhaled siRNA therapy targeting RAGE for pulmonary inflammation: a first-in-human randomized trial.

    Inhaled ARO-RAGE, a lung-epithelium-targeted siRNA against pulmonary RAGE mRNA, was safe and well tolerated in a first-in-human randomized trial in 58 healthy volunteers and 19 patients with asthma. Plasma levels were low, consistent with drug retention in the lung, and prolonged dose-responsive decreases in serum and bronchoalveolar lavage sRAGE indicated effective pulmonary target engagement. The results support continued clinical development of inhaled therapeutic siRNA for pulmonary inflammation.

    Why it matters: First-in-human data show an inhaled siRNA can safely engage a lung target with minimal systemic exposure.

Sep 3Thu
  1. Fierce Biotech50

    Ultragenyx fails phase 3 Angelman test, plots ‘significant expense reductions’

    Ultragenyx's phase 3 Aspire trial of apazunersen in Angelman syndrome missed its primary endpoint of change from baseline in Bayley-4 cognitive raw score and its secondary endpoint of net response on the Multidomain Responder Index. The company is reviewing the program's future and planning significant expense reductions. Shares fell 43% after hours; no trial figures were disclosed.

    Why it matters: A phase 3 failure in Angelman syndrome shifts prospects for a field with no approved disease-modifying treatments.

  2. 文献与产业新闻59

    Barcoded oligonucleotide system (BOLT) for targeted organ delivery

    BOLT is a barcoded oligonucleotide platform that lets many chemically diverse ligand-oligo conjugates be evaluated simultaneously in a single animal, combining rational barcode design, modular conjugation chemistry, and NGS-based quantification. It works in mice and nonhuman primates and identified ligands with tropism for brain, lung, and muscle, addressing the low throughput of testing oligo candidates one by one in animals. It changes how tissue-specific extrahepatic delivery ligands are screened.

    Why it matters: It offers a way to screen many oligo delivery ligands in vivo at once, in mice and nonhuman primates.

  3. Fierce Pharma36

    ARPA-H puts up $125M to bankroll personalized RNA-based drug production

    ARPA-H is investing $125 million to fund the production of personalized RNA drugs. The agency says that although RNA-based vaccines and therapeutics have recently faced headwinds in the U.S., the government remains optimistic about the field's prospects and continues large-scale investment. The funds will be dedicated to building manufacturing capacity for personalized RNA drugs.

    Why it matters: Not given.

Sep 1Tue
  1. Cell59

    Viral protease-initiated lytic cell death as a universal antiviral mRNA therapy.

    Gasdermin-D was engineered to carry viral protease-specific cleavage motifs, producing VID activators that trigger lytic cell death only in infected cells. Delivered as LNP-encapsulated mRNA in a hepatitis A virus model, they abolished viral replication and shedding in vivo and eased liver injury via a kill-and-alert mechanism, with activity also shown against Zika virus and SARS-CoV-2. Generative AI-designed cleavage motifs for the SARS-CoV-2 main protease improved antiviral potency.

    Why it matters: It turns viral protease activity into a broadly applicable mRNA kill-and-alert antiviral strategy.

  2. 顶刊论文（社媒热度）78

    Eplontersen for Transthyretin Amyloid Cardiomyopathy.

    Eplontersen, an antisense oligonucleotide that reduces hepatic transthyretin production, did not reduce cardiovascular death or recurrent cardiovascular events in transthyretin amyloid cardiomyopathy. In the phase 3 CARDIO-TTRansform trial, 1432 patients received subcutaneous eplontersen 45 mg or placebo every 4 weeks for 140 weeks; the primary composite occurred at a rate ratio of 0.89 (95% CI, 0.73 to 1.09; P = 0.28). The finding leaves no demonstrated outcome benefit for eplontersen on top of standard treatment in ATTR-CM.

    Why it matters: Negative phase 3 result for eplontersen in 1432 patients with ATTR-CM at 140 weeks.

  3. Nature Biotechnology71

    Enhanced antitumor immunity of mRNA vaccines by bioorthogonal-like delayed activation of exogeneous STING.

    Codelivered STING agonists suppress antigen mRNA translation, so the authors engineered Syn-STING, a lipid nanoparticle carrying antigen mRNA, mRNA encoding full-length STING and a DMXAA activator released on a delayed schedule via a biodegradable linker. In humanized STING mouse models with HPV E7 and ovalbumin antigens, the particles localized activation to myeloid antigen-presenting cells, avoided systemic regulatory B cell differentiation and immunocyte apoptosis, suppressed tumor growth and prolonged survival with negligible anti-STING immunity.

    Why it matters: It solves the problem that codelivered STING agonists blunt antigen mRNA translation in mRNA vaccines.

Aug 31Mon
  1. Science66

    Nonviral delivery of chemically modified tRNA rescues nonsense mutations in cystic fibrosis.

    Chemically modified suppressor tRNAs delivered by tailored lipid nanoparticles rescued nonsense mutations in cystic fibrosis. Adding N1-methyladenosine to sup-tRNAs improved premature termination codon readthrough, tRNA aminoacylation, functional persistence, and reduced innate immune activation. The LNP-delivered sup-tRNAs restored CFTR expression and function in bronchial epithelial cells, mouse models, and patient-derived organoids.

    Why it matters: Combines chemical tRNA modification with pulmonary LNP delivery to address the main barriers to sup-tRNA therapy.

  2. JAMA56

    Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy: A Meta-Analysis of Outcomes Trials.

    Pooled analysis of the phase 3 trials HELIOS-B and CARDIO-TTRansform (2086 patients with ATTR-CM) found TTR gene-silencing therapy cut the composite of all-cause mortality and recurrent cardiovascular events by 20% (RR, 0.80; 95% CI, 0.69-0.94), reduced all-cause death (HR, 0.74; 95% CI, 0.61-0.91), and preserved 6-minute walk distance (+22.2 m vs placebo). Benefit was significant in patients not on baseline TTR stabilizers (RR, 0.69) but not in those already receiving stabilizer therapy (RR, 0.97). The findings support TTR gene silencing for ATTR-CM and clarify how background stabilizer use shapes the treatment effect.

    Why it matters: It quantifies the overall effect of TTR gene silencers in ATTR-CM and shows benefit depends on baseline stabilizer use.

Aug 30Sun
  1. Nature59

    Eplontersen with and without background transthyretin stabilizers in transthyretin amyloid cardiomyopathy: secondary analysis of a phase 3, randomized controlled trial

    A secondary analysis of the CARDIOTTRansform phase 3 randomized controlled trial found that eplontersen, a transthyretin-targeting antisense oligonucleotide, benefited patients with transthyretin amyloid cardiomyopathy who were not on transthyretin stabilizers at baseline, but showed no such effect in those already taking stabilizers. The result separates responders from non-responders by background therapy. Findings were presented at the 2026 ESC Congress.

    Why it matters: It identifies baseline transthyretin stabilizer use as a factor determining which cardiomyopathy patients benefit from eplontersen.

Aug 29Sat
  1. BioCentury67

    Can silencers add benefit in ATTR-CM?

    Eplontersen, co-developed by AstraZeneca and Ionis, missed the primary endpoint in the Phase III CARDIO-TTRansform trial in ATTR-CM. Detailed data show that among patients already on a TTR stabilizer at baseline, adding eplontersen led to worse outcomes than the stabilizer alone. The miss, announced in July, is a major setback for a planned future core revenue driver for both companies.

    Why it matters: Subgroup data showing worse outcomes with added eplontersen rule out combination use in patients already on TTR stabilizers.

  2. WeChat71

    Li Bowen Team Restores Prematurely Terminated Protein Synthesis with Nonviral Delivery of Chemically Modified tRNA in Science

    BioArt reports on a Science study by Bowen Li's team, which used nonviral delivery of chemically modified tRNA to restore protein synthesis interrupted by premature stop codons. The source cites only the 2023 Nobel Prize to Karikó and Weissman for nucleoside modifications as background, noting that different RNAs require their own modification recipes, and provides no specific experimental data.

    Why it matters: The source reports a nonviral strategy delivering chemically modified tRNA to restore prematurely terminated protein synthesis, useful for comparison with existing tRNA therapies.

Aug 28Fri
  1. The Lancet61

    Safety and lipoprotein(a)-lowering effects of Kylo-11, a non-canonical, long-duration small interfering RNA targeting lipoprotein(a): a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial.

    A single subcutaneous dose of Kylo-11, a very long-acting small interfering RNA targeting lipoprotein(a), cut median serum lipoprotein(a) by up to -97% at 48 weeks in healthy adults with elevated concentrations, with reductions of -53% at 9 mg and -96% in participants above 200 nmol/L given 225 mg. In the 70 dosed participants, adverse events occurred in 53%, mostly grade 1-2 and deemed unrelated; there were no serious or drug-related events. The findings support durable lipoprotein(a) lowering from one dose.

    Why it matters: It shows a single siRNA dose can durably lower lipoprotein(a) for up to 48 weeks in humans.

Aug 27Thu
  1. WeChat80

    GSK's bepirovirsen approved in Japan as world's first functional cure therapy for hepatitis B

    Japan approved GSK's antisense oligonucleotide bepirovirsen (brand name Hibsago) on August 24, 2026 for functional cure of chronic hepatitis B in adults previously treated with nucleos(t)ide analogues who have HBsAg levels of 3000 IU/mL or below. It is the first approved functional cure therapy for hepatitis B worldwide, moving treatment from lifelong viral suppression toward finite-course cure. China has an estimated 75 million people living with hepatitis B infection.

    Why it matters: First-ever approved functional cure for hepatitis B marks a shift from lifelong suppression therapy.

Aug 26Wed
  1. WeChat74

    Japan Approves GSK Antisense Drug Hibsago for Functional Cure of Chronic Hepatitis B

    Japan's Ministry of Health, Labour and Welfare has approved GSK's antisense oligonucleotide therapy Hibsago (bepirovirsen) as a functional cure treatment for chronic hepatitis B, the first such regimen in Japan. It applies to adults previously treated with nucleos(t)ide analogues for at least 6 months who meet predefined virological marker criteria.

    Why it matters: First approved functional cure therapy for chronic hepatitis B in Japan, a new option for a large patient population.

  2. WeChat83

    Japan Approves GSK's Bepirovirsen as World's First Functional Cure for Hepatitis B

    Japan's Ministry of Health, Labour and Welfare approved GSK's antisense oligonucleotide bepirovirsen (brand name Hibsago) on August 24, 2026, as a functional cure for chronic hepatitis B. It is the first approval worldwide for the drug and the first approved functional cure therapy for CHB, covering adults previously treated with nucleos(t)ide analogues for at least six months who meet viral marker criteria. The disease affects about 240 million people globally, including about 75 million in China.

    Why it matters: First-ever global approval of a functional cure for chronic hepatitis B shifts treatment options for millions of patients.

Aug 25Tue
  1. WeChat80

    GSK's antisense drug bepirovirsen approved in Japan for functional cure of chronic hepatitis B

    GSK's antisense oligonucleotide drug bepirovirsen (Hibsago) has been approved in Japan for adults with chronic hepatitis B who received at least six months of nucleos(t)ide analogue therapy and met predefined virological criteria, aiming at functional cure. The approval is based on the Phase III B-Well study. Marketing applications are under review in China, the US and the EU.

    Why it matters: First worldwide approval of a first-in-class ASO aiming at functional cure of chronic hepatitis B.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org