Jun 2026· Nucleic Acid Insights· Vol 3, pp. 333–337· 0 citations
TL;DR
Across April and May 2026, the nucleic acid therapeutics field saw broad regulatory momentum, continued clinical advancement, and significant manufacturing investment, with AI-driven drug discovery also advanced.
Abstract
Across April and May 2026, the nucleic acid therapeutics field saw broad regulatory momentum, continued clinical advancement, and significant manufacturing investment. Regulatory highlights included MHRA authorisation of the ligand-conjugated ASO donidalorsen for hereditary angioedema prophylaxis and US FDA acceptance of GSK's NDA for the ASO bepirovirsen in chronic hepatitis B, the latter also receiving Breakthrough Therapy Designation. Clinical milestones featured the 50th patient treated under n-Lorem Foundation's personalized ASO programme and first results from HF-REVERT, the inaugural randomized trial of microRNA inhibition in heart failure. Manufacturing expansion featured prominently, with both Agilent Technologies and WuXi AppTec announcing major capacity increases for oligonucleotide production. AI-driven drug discovery also advanced, with RareLabs launching a robotics- and AI-enabled platform for rare disease ASO and siRNA development, and Ribo Life Science partnering with Insilico Medicine to integrate AI across its siRNA pipeline.
May and June 2026 saw significant clinical and regulatory momentum across nucleic acid therapeutic modalities. Regulatory highlights included FDA Breakthrough Therapy Designation for Biogen’s intrathecally administered ASO salanersen in spinal muscular atrophy and MHRA authorisation of Moderna and the University of Oxford’s INTERCEPT-Lynch Phase 1/2 trial of mRNA-4194, the first investigational mRNA cancer prevention vaccine. In clinical development, Novartis reported positive Phase 1/2 biomarker data for the AOC del-brax in facioscapulohumeral muscular dystrophy, GSK published Phase 3 data demonstrating a 19% functional cure rate for the ASO bepirovirsen in chronic hepatitis B, and SpliSense secured $13 million from the Cystic Fibrosis Foundation to advance inhaled ASO SPL84 into Phase 2b. Strategic activity included a multi-target ASO collaboration between Servier and n-Lorem Foundation in rare neurodevelopmental disorders, and WuXi AppTec’s announcement of a 17% increase in capital expenditure to expand oligonucleotide and peptide manufacturing capacity globally.
Small interfering RNA (siRNA) therapeutics represent a paradigm shift in targeting previously undruggable diseases through specific gene silencing. Since the FDA's first approval of patisiran in 2018, the field has expanded rapidly, with eight approved drugs and numerous clinical candidates. However, the atypical pharmacokinetic-pharmacodynamic (PK-PD) profile of siRNAs, characterized by rapid plasma elimination, prolonged tissue retention, and temporal dissociation between exposure and effect, has created distinct obstacles for conventional dose-finding strategies. This review examines how model-informed drug development, particularly pharmacometric modeling, has emerged as an essential tool in the advancement of siRNA therapeutics. Population PK-PD models for all FDA-approved siRNA drugs are systematically described, demonstrating that mechanistic and semi-mechanistic approaches inform preclinical-to-clinical translation, optimize dosing regimens, and support regulatory decisions. Key modeling frameworks include: (1) mechanistic models incorporating asialoglycoprotein receptor (ASGPR)-mediated uptake, RNA-induced silencing complex (RISC) loading, and mRNA degradation kinetics; (2) minimal physiologically-based PK-PD models for interspecies scaling; and (3) exposure-response models addressing the disconnect between plasma PK and pharmacological activity. This review also discusses how quantitative pharmacology addresses developmental challenges, including first-in-human dose selection, optimal dosing intervals, organ impairment effects, and interindividual variability. This pharmacometric perspective provides a quantitative framework for rational development of safe and effective siRNA therapeutics across diverse patient populations.
Jueun Kang, H. Yim, H. Jeong et al.· Current Gene Therapy· 0 citations
Dear Reader,
For decades the Indian Pharmaceutical Industry has proudly worn the mantle of the “Pharmacy of the World” driven by an unparalleled mastery of small molecules, using efficient manufacturing and chemical synthesis. However, as the global therapeutic landscape rapidly shifts to large molecules, precision biotherapeutics, cell and gene therapy we find ourselves at a critical inflection point. The year 2026 marks a significant milestone in Indian biopharma policy. The recent BioE3 policy and Biopharma SHAKTI initiative, with its Rs.10,000/- crore outlay signals a definitive pivot from volume driven growth to value driven innovations in the move to much needed affordable next generation biologics. The goal is to explicitly reduce import dependence, build shared clinical trial infrastructure and capture a significant share of the global biopharmaceutical market. While blockbuster biologics offer a massive window of opportunity, capitalizing on it requires more than manufacturing scale. It demands integration of advanced biologic technology, rigorous clinical evaluation and an end to end bio-manufacturing ecosystem.
Small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) have emerged as clinically validated therapeutic modalities, with approvals and late‐stage development programs spanning rare genetic, neurologic, cardiovascular, metabolic, and infectious diseases. Despite these advances, oligonucleotide development presents unique challenges compared with small molecules and biologics, including rapid plasma distributive clearance, nuclease‐mediated degradation, limited extrahepatic distribution, and prolonged pharmacodynamic effects driven by tissue retention and intracellular mechanisms such as RNA‐induced silencing complex loading or RNase H‐mediated activity. Consequently, tissue disposition and intracellular pharmacology most often govern therapeutic response more directly than plasma exposures alone, complicating conventional approaches to dose selection, efficacy prediction, and safety assessment. Model‐informed drug development (MIDD) offers a quantitative framework to address these challenges through integration of preclinical, translational, and clinical data into empirical, mechanistic, and systems‐level models. This review summarizes current and emerging MIDD applications in oligonucleotide therapeutics, with primary emphasis on siRNAs and complementary insights from ASOs. Approaches discussed include empirical and semi‐mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, physiologically based pharmacokinetic (PBPK) frameworks describing tissue‐selective biodistribution and intracellular disposition, and quantitative systems pharmacology (QSP) models linking molecular target modulation with downstream biologic and clinical responses. Collectively, these approaches have supported cross‐species translation; human dose selection; clinical trial optimization; and mechanistic understanding of oligonucleotide absorption, distribution, metabolism, excretion, and pharmacology. Finally, we discuss future opportunities and remaining challenges for MIDD in oligonucleotide therapeutics, including enabling extrahepatic delivery, characterizing interindividual variability, and integrating systems‐level and data‐driven approaches to improve translational predictability and accelerate development of next‐generation oligonucleotide medicines.
Paridhi Gupta, Mindy Magee, Vivaswath S. Ayyar· Journal of clinical pharmaco...· 0 citations
The principles that shape cardiovascular ASO candidate development are discussed, with emphasis on mechanism selection, chemical design, and exposure feasibility, and sequence optimization with exposure-informed target qualification and therapeutic-index engineering throughout ASO candidate selection.
D. Park, A. Bühler, Christian Schöllhorn et al.· Expert Opinion on Drug Disco...· 0 citations
July 2026 saw the field push access outward on multiple fronts, from the first FDA approval of a genetic therapy for children as young as 2 years (Vertex’s CASGEVY) to the first international patient treated with satri‑cel, the first CAR‑T therapy approved anywhere for a solid tumor. Regulatory momentum extended across in vivo CAR‑T, allogeneic transplant, and solid tumor cell therapy, while ARPA‑H committed up to $160 million to scalable in vivo gene editing for rare diseases. Alongside these milestones, new partnerships, a €33 million financing, and first patient dosings in pivotal trials for Gaucher disease type 1 and diabetic retinopathy signaled continued investment across the manufacturing, clinical, and commercial landscape.
Abigail Pinchbeck· Cell and Gene Therapy Insigh...· 0 citations