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Lipid Nanoparticle Research News: July 1-28, 2025


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News Summary

Nagoya University: New cyclic disulfide lipids deliver mRNA five times more effectively for cancer treatment

University of Ottawa: Development of nano-sized delivery agents with therapeutic potential beyond messenger function

University of Pennsylvania: Chemical modification of ionizable lipids reduces inflammation and boosts mRNA therapeutic effectiveness

Academic Journals: Multiple publications on circular guide RNA engineering, CRISPR-Cas13d systems, and advanced LNP characterization methods

PreciGenome Flex System: Featured in research on circular guide RNA and CRISPR-Cas13d-encoding mRNA for triple-negative breast cancer immunotherapy

Market Analysis: Global lipid nanoparticles market projected to reach $3.84 billion by 2034, expanding at 13.97% CAGR

CDMO Market: Lipid nanoparticles contract development and manufacturing organization market expected to witness double-digit growth by 2027

Clinical Research: Advanced studies on cellular barriers to LNP-mediated RNA delivery and mechanistic improvements

Technology Developments: New formulation methods, automated screening platforms, and precision targeting approaches

Regulatory Progress: European Medicines Agency and European Pharmacopoeia updating guidelines for LNP-based medicines


Detailed News Coverage

Breakthrough Cancer Treatment Technology

Nagoya University researchers developed revolutionary cyclic disulfide lipids that deliver mRNA to cells five times more effectively than conventional methods, marking a significant advance in cancer treatment approaches. This breakthrough addresses long-standing challenges in mRNA delivery efficiency and represents a major step forward in therapeutic applications.

The modified lipid nanoparticle (CDL-LNP) contains several ingredients that work together to deliver mRNA effectively: the mRNA payload with genetic instructions, standard lipid molecules (ionizable lipids, phospholipids, cholesterol, PEG-lipids) that form the particle structure, and the new cyclic disulfide lipids (CDL) that help the mRNA escape from cellular traps once inside the cell. Credit: Kimura et al., 2025
The modified lipid nanoparticle (CDL-LNP) contains several ingredients that work together to deliver mRNA effectively: the mRNA payload with genetic instructions, standard lipid molecules (ionizable lipids, phospholipids, cholesterol, PEG-lipids) that form the particle structure, and the new cyclic disulfide lipids (CDL) that help the mRNA escape from cellular traps once inside the cell. Credit: Kimura et al., 2025

Release Date: July 28, 2025

Authors: Seigo Kimura, Kana Okada, et al.

Related Institution: Nagoya University

Location: Nagoya, Japan


The University of Ottawa announced development of nano-sized delivery agents that possess therapeutic potential beyond traditional messenger functions. This research expands the conceptual framework for nanoparticle applications, suggesting these systems can serve both delivery and therapeutic roles simultaneously.

Thunder fluorescence microscopy image showing endosomal colocalization of SM3d-LNP (NBD-cholesterol) with late endosomal marker (RAB7) in RAW macrophages. Cells were fixed and stained with antibodies against NBD-C SM3d (green), RAB7 (late endosome marker, pink). DAPI (blue) was added for nuclei, which were labeled. Merged images reveal areas of colocalization, such as White (NBD-C SM3d (green) +RAB7 (pink)). Credit: ACS Applied Nano Materials (2025). DOI: 10.1021/acsanm.4c06802
Thunder fluorescence microscopy image showing endosomal colocalization of SM3d-LNP (NBD-cholesterol) with late endosomal marker (RAB7) in RAW macrophages. Cells were fixed and stained with antibodies against NBD-C SM3d (green), RAB7 (late endosome marker, pink). DAPI (blue) was added for nuclei, which were labeled. Merged images reveal areas of colocalization, such as White (NBD-C SM3d (green) +RAB7 (pink)). Credit: ACS Applied Nano Materials (2025). DOI: 10.1021/acsanm.4c06802

Release Date: July 22, 2025

Authors: Shireesha Manturthi, Amandine Courtemanche, et al.

Related Institution: University of Ottawa

Location: Ottawa, Ontario, Canada


Chemical Innovation in LNP Design

University of Pennsylvania scientists achieved a major breakthrough by tweaking the structure of ionizable lipid components in LNPs, successfully reducing side effects such as inflammation while boosting the effectiveness of mRNA-based therapeutics and vaccines. The key innovation involves adding phenol groups with documented anti-inflammatory properties.

The research team utilized the Mannich reaction, combining three precursors instead of the traditional two-component approach, enabling creation of hundreds of new lipids. This method represents a significant departure from conventional synthesis approaches and demonstrates the potential for enhanced therapeutic outcomes with reduced immunogenicity.

Release Date: July 18, 2025

Authors: Michael Mitchell, Ninqiang Gong, et al.

Related Institution: University of Pennsylvania

Location: Philadelphia, Pennsylvania, United States


Advanced CRISPR-Cas13d Applications

A groundbreaking study published on bioRxiv details the engineering of circular guide RNA and CRISPR-Cas13d-encoding mRNA for RNA editing of Adar1 in triple-negative breast cancer immunotherapy. This research addresses critical limitations in current CRISPR-Cas systems by developing highly stable circular gRNAs (cgRNAs) that resist degradation. The study demonstrates that cgRNAs enhance biostability with comparable Cas13d-binding affinity relative to linear gRNA. Using the PreciGenome Flex-S system for LNP preparation, researchers co-delivered Adar1-targeting cgRNA with mRNA encoding RfxCas13d to triple-negative breast cancer cells, achieving significant improvements in target gene knockdown efficiency.

Release Date: July 22, 2025

Authors: Shurong Zhou, Suling Yang, Jie Xu, Guizhi Zhu

Related Institution: University of Michigan College of Pharmacy

Location: Ann Arbor, Michigan, United States


Market Growth and Commercial Development

The global lipid nanoparticles market size reached $1.18 billion in 2025 and is projected to grow at a compound annual growth rate of 13.97% between 2025 and 2034, reaching approximately $3.84 billion by 2034. This expansion is driven by advancements in lipid nanoparticle-based drugs, increased use in cancer treatments and mRNA therapies, and rising prevalence of chronic diseases.

Release Date: July 2025


Meanwhile, the contract development and manufacturing organization (CDMO) market for lipid nanoparticles is positioned for substantial double-digit growth by 2027, driven by growing acceptance of LNPs in mRNA therapeutics and aggressive investments by private equity firms.

Release Date: July 10, 2025


Mechanistic Research and Barriers

Researchers published comprehensive analysis of cellular and biophysical barriers to lipid nanoparticle-mediated delivery of RNA to the cytosol. Using live-cell and super-resolution microscopy, scientists identified multiple distinct steps of inefficiencies in cytosolic delivery of both siRNA and mRNA cargoes.


The study revealed that membrane damages marked by galectin recruitment are conducive to cytosolic RNA release, while membrane perturbations recruiting ESCRT machinery do not permit endosomal escape. These findings provide crucial insights for optimizing LNP formulations and improving therapeutic efficiency.

HeLa cells expressing YFP-Galectin-9 (HeLa-Gal9-YFP) were incubated with fluorescently labeled siRNA- or mRNA-LNPs during live-cell widefield microscopy. a Representative images showing galectin-9 response and LNP uptake after 100 min continuous incubation with 100 nM siRNA-LNP or 1.5 µg mL–1 mRNA-LNP. Brightness and contrast were adjusted separately. Outlines indicate cell boundaries; color bar shows intensity value range. Images are representative of 106 and 102 cells from two independent experiments. Scale bar is 10 µm. b Number of galecin-9 foci per cell evaluated during 8 h LNP incubation. Line is mean, shade is s.d. N = 4 technical replicates, see Methods for N details. c Representative images showing de novo recruitment of galectin-9 to a vesicle containing siRNA-LNP (top) and mRNA-LNP (bottom), indicated by arrowheads. Time = 0 is the first frame with detectable galectin recruitment. Scale bar is 1 µm. d Fluorescence intensity of vesicles containing AF647-siRNA-LNP or Cy5-mRNA-LNP before detectable membrane damage. Circles are vesicles pooled from 2–4 independent experiments per condition. Number of vesicles (Nv) and cells (Nc) analyzed were (Nv;Nc) = (115;81), (84;61), (170;82), (315;111) and (117;87) for 4, 10, 20, 50 nM siRNA-LNP and 0.75 µg mL–1 mRNA-LNPs, respectively. Boxes are median ± i.q.r.; whiskers are 10–90 percentiles. e Fraction of all damaged vesicles with detectable siRNA or mRNA payload. Bars are mean, error bars are s.d. N = 3 independent experiments. Statistics: Brown-Forsythe and Welch ANOVA with two-tailed Dunnett’s T3 multiple comparisons test. f Fluorescence intensity of individual RNA+ vesicles around the time of membrane damage (t = 0). Traces were sub-grouped to identify events with fast initial RNA release. Yellow star: all events. Magenta star: fast releasing vesicles vs. other vesicles. Lines are median, shades are 95% CI of median. Bars (top) show fraction of fast releasing vesicles vs. other vesicles. Data are pooled from 2–4 independent experiments per condition.
HeLa cells expressing YFP-Galectin-9 (HeLa-Gal9-YFP) were incubated with fluorescently labeled siRNA- or mRNA-LNPs during live-cell widefield microscopy. a Representative images showing galectin-9 response and LNP uptake after 100 min continuous incubation with 100 nM siRNA-LNP or 1.5 µg mL–1 mRNA-LNP. Brightness and contrast were adjusted separately. Outlines indicate cell boundaries; color bar shows intensity value range. Images are representative of 106 and 102 cells from two independent experiments. Scale bar is 10 µm. b Number of galecin-9 foci per cell evaluated during 8 h LNP incubation. Line is mean, shade is s.d. N = 4 technical replicates, see Methods for N details. c Representative images showing de novo recruitment of galectin-9 to a vesicle containing siRNA-LNP (top) and mRNA-LNP (bottom), indicated by arrowheads. Time = 0 is the first frame with detectable galectin recruitment. Scale bar is 1 µm. d Fluorescence intensity of vesicles containing AF647-siRNA-LNP or Cy5-mRNA-LNP before detectable membrane damage. Circles are vesicles pooled from 2–4 independent experiments per condition. Number of vesicles (Nv) and cells (Nc) analyzed were (Nv;Nc) = (115;81), (84;61), (170;82), (315;111) and (117;87) for 4, 10, 20, 50 nM siRNA-LNP and 0.75 µg mL–1 mRNA-LNPs, respectively. Boxes are median ± i.q.r.; whiskers are 10–90 percentiles. e Fraction of all damaged vesicles with detectable siRNA or mRNA payload. Bars are mean, error bars are s.d. N = 3 independent experiments. Statistics: Brown-Forsythe and Welch ANOVA with two-tailed Dunnett’s T3 multiple comparisons test. f Fluorescence intensity of individual RNA+ vesicles around the time of membrane damage (t = 0). Traces were sub-grouped to identify events with fast initial RNA release. Yellow star: all events. Magenta star: fast releasing vesicles vs. other vesicles. Lines are median, shades are 95% CI of median. Bars (top) show fraction of fast releasing vesicles vs. other vesicles. Data are pooled from 2–4 independent experiments per condition.

Release Date: July 1, 2025

Authors: Johanna M. Johansson, Hampus Du Rietz, et al.

Related Institution: Lund University

Location: Lund, Sweden


Advanced Formulation Technologies

Frontiers in Medical Technology published research on enhancing nucleic acid delivery through integration of artificial intelligence with LNP development. The comprehensive review explores evolution and design of LNPs, focusing on their role in hematologic therapies and platelet transfection applications. The study systematically evaluates LNP composition, highlighting roles of ionizable, cationic, and neutral lipids in optimizing delivery efficiency, stability, and immune response modulation. Advanced artificial intelligence integration represents a significant step toward predictive nanoparticle design.


Overview of Lipid Nanoparticles (LNPs) for Nucleic Acid Delivery. Structure: A 3D-rendered schematic showing an LNP particle. Core: Encapsulated nucleic acid (e.g. mRNA) shown as a helical structure. Lipids: Layers illustrating cationic lipids (binding to nucleic acids) ionizable lipid (to aid endosomal escape), helper lipids, cholesterol, and PEG-lipids on the outer surface for circulation stability.
Overview of Lipid Nanoparticles (LNPs) for Nucleic Acid Delivery. Structure: A 3D-rendered schematic showing an LNP particle. Core: Encapsulated nucleic acid (e.g. mRNA) shown as a helical structure. Lipids: Layers illustrating cationic lipids (binding to nucleic acids) ionizable lipid (to aid endosomal escape), helper lipids, cholesterol, and PEG-lipids on the outer surface for circulation stability.

Release Date: June 16, 2025

Authors: Kagya Amoako, Amir Mokhammad, Afrida Malik, et al.

Related Institutions: University of New Haven; Yale University; University of North Carolina, Chapel Hill

Locations: West Haven, Connecticut, United States; New Haven, Connecticut, United States; Chapel Hill, North Carolina, United States


Clinical Translation Progress

Duke University researchers developed an mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy. The innovative system, termed LiNx, incorporates LNPs loaded with mRNA encoding tumor antigens, demonstrating substantial immune cell recruitment and antigen presentation capabilities. The LiNx system generates potent immune responses with a single dose comparable to conventional three-dose LNP immunization protocols, while promoting distinct Type 17 T helper cell responses critical for enhanced antitumor efficacy.

Release Date: July 2025

Authors: Zhu, Yining, Yao, Zhi-Cheng, et al.

Related Institution: Duke University

Location: Durham, North Carolina, United States


Manufacturing and Process Innovation

Solid lipid nanoparticles continue to gain attention as innovative drug delivery systems, with a comprehensive AAPS review published examining preparation techniques, excipient formulations, and manufacturing models. The review highlights prospects for surface modification, enhanced penetration across biological barriers, chemical resistance, and capacity to encapsulate multiple therapeutic substances simultaneously, all relevant for clinical applications.

Release Date: July 8, 2025

Authors: Kaushal Aggarwal, Sachin Joshi, et al.

Related Institution: ISF College of Pharmacy

Location: Punjab, India


Emerging Applications and Novel Approaches

Research teams explore expanding applications beyond traditional vaccine delivery, including targeted protein therapies, gene editing platforms, and personalized medicine approaches. These developments represent significant evolution from early LNP applications toward comprehensive therapeutic platforms. Studies examine strategies to improve mRNA stability and translational efficiency, including formulation stabilization through lyophilization, novel materials such as poly(beta-amino esters), and hybrid nanoparticle systems designed to enhance delivery efficiency while reducing toxicity.

Release Date: July 14, 2025

Authors: Aljoscha Gabelmann, Achim Biesel, Brigitta Loretz, Claus-Michael Lehr

Related Institutions: Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS); Helmholtz-Centre for Infection Research (HZI); Saarland University

Location: Saarbrücken, Germany

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