Explore recent mRNA, saRNA, circular RNA, and LNP research on delivery, therapeutic translation, safety, analytical characterization, and manufacturing.
Selected for substantive contributions to delivery, translation, analytics, manufacturing, and safety. Original publication dates and evidence levels are retained. This library covers the latest 120 days; individual published guides remain available.
Biesel A; Shandheep A; Pavlou A; Busker LM; Koch M; Kopliku V; Maisel K; Boese A; Skerra J; Schröder LJ; Neubert L; Schneider-Daum N; Loretz B; Kalinke U; Lehr CM Journal of controlled release : official journal of the Controlled Release Society · DOI 10.1016/j.jconrel.2026.115509
Lipid-polymer hybrid particles combined polymer stability with lipid-mediated transfection. Hyaluronic acid and polyvinyl alcohol coatings helped preserve particle properties after nebulization, while mucus-covered airway cultures retained measurable transfection. Primary human lung fibroblasts and intratracheally dosed mice provided additional delivery evidence. These results support aerosol formulation development, although intratracheal dosing does not establish the performance of inhaled aerosols in patients.
Why it is included: Addresses both aerosol stress and airway barriers; inhalation deposition, repeated dosing, and disease-specific efficacy remain important translation gaps.
Jinbi Tian; Khanh T. M. Tran; Brett H. Pogostin; Olivia Sheridan; Sevinj Mursalova; Amy H. Lee; Shuai Liu; Jaya Hamkins; Daniel Antov; Alana L. Power; Zane S. Dash; Dongsoo Yun; Mina Konaković Luković; Robert S. Langer; Ana Jaklenec Nature Biotechnology · DOI 10.1038/s41587-026-03331-w
The AGENT platform combines Bayesian optimization with high-throughput experiments to identify thermostable mRNA-LNP formulations through six iterations in approximately one month. Solid-state model formulations based on SM-102 and ALC-0315 retained biological activity after more than two months at 37°C. Animal immunogenicity supported further development, but these formulation-specific findings do not eliminate cold-chain requirements for mRNA products generally.
Why it is included: Illustrates efficient formulation optimization for thermostability; real products require long-term potency, transport, reconstitution, and safety data under their intended conditions.
Zixuan Zhen; Mittal Darji; Kuo-Chih Shih; Xinhao Lin; Rama Prajapati; Sheyda Ranjbar; Nirnoy Dan; Grace Shenouda; Jonathan Hu; Robin Bogner; Xiuling Lu Journal of Controlled Release · DOI 10.1016/j.jconrel.2026.115412
Researchers compared 12 lyophilized mRNA-LNP formulations containing sucrose, trehalose, and polyvinylpyrrolidone. A ternary protectant system at a 1:20 lipid-to-protectant ratio preserved particle properties, RNA integrity, and in vitro transfection after one month at 40°C. Sucrose crystallization reduced protection. The results show why physical measurements need functional confirmation and do not establish a clinical product shelf life.
Why it is included: Links protectant physical state with functional stability; formulation developers should combine particle and RNA measurements with potency under relevant storage conditions.
Kinnari Santosh Arte; Rachana Sapkota; Chanakya D. Patil; Yijing Huang; Eric J. Munson; Sajal Patel; Nicole Payton; Rushit Lodaya; Qi Tony Zhou; Li Lily Qu AAPS PharmSciTech · DOI 10.1208/s12249-026-03516-1
Using yeast RNA as a model payload, researchers evaluated atomization, freezing, drying temperature, and annealing during spray-freeze drying of RNA-LNPs. Powder diffraction, microscopy, and solid-state NMR supported characterization. Sucrose outperformed trehalose in the tested systems, and annealing improved stability. Because the payload was model RNA, these findings do not directly establish therapeutic mRNA expression potency or clinical-product stability.
Why it is included: Offers process guidance for solid RNA formulations; therapeutic mRNA translation requires additional integrity, functional potency, and product-specific stability studies.
This CMC review connects lipid chemistry and manufacturing parameters with critical quality attributes in mRNA-LNP development. It compares microfluidic scale-out with impinging-jet scale-up and emphasizes orthogonal analytics, stability in plasma or serum, lipid impurities, and RNA–lipid adducts. Early comparability planning is recommended. The framework does not demonstrate that one carrier or manufacturing platform is universally superior.
Why it is included: Helps connect discovery formulations with development requirements; particle size and encapsulation alone cannot establish a complete manufacturing control or comparability strategy.
Shu Zhang; Yaxi Li; Aygun Teymur; Bowen Yang; Sheereen Majd; Chandra Mohan; Tianfu Wu ACS Biomaterials Science & Engineering · DOI 10.1021/acsbiomaterials.6c00494
A mannose-containing fifth lipid was incorporated into spleen-targeted LNPs to combine endogenous organ enrichment with receptor-associated uptake. Adjusting mannose-lipid content shifted distribution toward the spleen and improved macrophage transfection. Experiments identified uptake by macrophages and conventional dendritic cells, alongside freeze-thaw stability testing. These findings support immune-delivery development, while therapeutic and human targeting performance remain undetermined.
Why it is included: Combines ligand targeting and organ-selective formulation in one platform; uptake enrichment alone does not establish clinical immunotherapy efficacy.
This review compares liquid chromatography and mass spectrometry strategies for quantifying ionizable lipids, PEG lipids, helper phospholipids, cholesterol, and degradation products in mRNA-LNP formulations. It considers sensitivity, linearity, run time, matrix effects, and stability-indicating measurements. The comparison supports method selection rather than demonstrating a single validated release assay applicable to every formulation.
Why it is included: Connects lipid composition with degradation monitoring; developers must establish formulation-specific suitability, recovery, and validation rather than relying on a generic lipid assay.
Yunhe Su; Joseph Choy; Xiang Liu; Yining Zhu; Jinghan Lin; Christine Wei; Kailei D. Goodier; Di Yu; Leonardo Cheng; Milan Patel; Xiaoya Lu; Jingyao Ma; Jialiang Wang; Hai-Quan Mao ACS Applied Materials & Interfaces · DOI 10.1021/acsami.6c06888
Acid-cleavable cholesterol-derived crosslinkers and PEG-diamines stabilized anionic LNPs that otherwise lost activity during purification. By tuning crosslinking architecture, researchers balanced structural integrity with RNA release and improved splenic mRNA expression. Mechanistic analyses implicated intracellular processing as well as release behavior. These formulation-specific animal results do not establish general T-cell targeting or clinical manufacturing readiness.
Why it is included: Expands accessible anionic formulation space for spleen delivery; crosslinker clearance, repeat dosing, and manufacturing comparability still need evaluation.
