Papers, explained in our own words

217. mRNA encoding norovirus VP1 produces antigenically functional virus-like particles in vitro

Reyes Ballista Jm, David C, Pirrone A, Gonzalez-Fernandez E, Wei J, Wen Z

Human norovirus is a leading cause of acute gastroenteritis worldwide across all age groups, yet no licensed vaccine is available. The major capsid protein, VP1, self-assembles into highly immunogenic virus-like particles (VLPs) that have shown promise in clinical studies. Recently, mRNA has emerged as a compelling…

• Norovirus VP1
• Virus-like particle formation
• mRNA vaccine

218. 19F MRI-Traceable PLGA Nanocarriers: Influence of Particle Architecture on Co-Encapsulation and Release of Immiscible Payloads

Larreina Vicente N, Lodrini A, Groeneveld E, Tagit O, Goumans Mj, Srinivas M

Two perfluorocarbon (PFC)-loaded PLGA nanoparticles (NPs) of different architectures were previously established as 19F MRI tracers: sodium cholate (NaCh)-stabilized core-shell particles (CSPs) and PVA-stabilized multicore particles (MCPs). Differing in their stabilizers and internal PFC distribution, they exhibited…

• controlled release
• image-guided drug delivery
• multiphasic systems
• particle architecture
• perfluorocarbons
• polymer nanoparticles
• theranostics

219. Plant-derived extracellular vesicles in cell-free therapeutics for neurological diseases

Gu C, Chen M, Li Y, Lai Y, Xu Y, Dong Q, Et Al.

Plant-derived extracellular vesicles offer a promising frontier in nanomedicine for managing neurological diseases. This review systematically addresses their classification, botanical sources, isolation techniques, and biogenesis pathways. Comprehensive compositional analyses reveal a diverse cargo of proteins…

• cell-free
• fruit
• herb
• neural regeneration
• neurological diseases
• plant-derived extracellular vesicles
• therapeutics
• vegetable

220. A minimally modified AAV9 variant (AAV9fyhr) for enhanced CNS gene delivery by intra-CSF administration

Garza It, Ramesh V, Hu Y, Rioux M, Takar M, Higgs H, Et Al.

Adeno-associated virus (AAV) mediated gene therapies continue to show promise for the treatment of genetic diseases. However, delivery and safety still represent significant prohibitive barriers restricting translation of these delivery modalities to humans. We describe a novel AAV9 variant, "AAV9fyhr" or "FYHR"…

221. Machine learning-guided chondrocyte membrane-camouflaged lipid nanoparticles for intra-articular SOX9 mRNA therapy of osteoarthritis

Li J, Li C, Wang H, Yu H, Zhang T, Li C, Et Al.

Osteoarthritis (OA) progression involves cartilage matrix loss and persistent inflammation. This study developed a machine learning-guided and chondrocyte membrane-camouflaged lipid nanoparticle carrying messenger RNA (CM-LNP@mRNA) platform for intra-articular SOX9 delivery. Random forest analysis identified the…

• Biomimetic drug delivery
• Lipid nanoparticles
• Machine learning
• Messenger RNA
• Osteoarthritis

222. MYD88-silencing hUCMSC-derived extracellular vesicles alleviate sepsis- associated encephalopathy by modulating neurovascular and microglial inflammation

Fan M, Yang W, Lei F, Liu M, Wang R, Shen Y, Et Al.

Background: Sepsis-associated encephalopathy (SAE) is a common complication of sepsis and is closely associated with persistent neuroinflammation, neurovascular injury and long-term cognitive impairment. Myeloid differentiation primary response 88 (MYD88) is a shared signaling adaptor for the Toll-like receptor…

223. In Vivo CRISPR Screen Identifies RPS19 as an Immunotherapy Target in Hepatocellular Carcinoma

He L, Yu D, Xie F, Hou K, Li Z, Dai M, Et Al.

Despite the remarkable clinical success of immunotherapy, its efficacy against hepatocellular carcinoma (HCC) remains severely limited, highlighting an urgent need for novel targets and strategies to overcome immune evasion. Here, we aimed to identify key regulators of HCC immunity via unbiased functional screening…

• CRISPR screens
• RPS19
• gene editing
• hepatocellular carcinoma
• tumor immunotherapy

224. CRISPR-based functional screening of noncoding regulatory elements

Roh H, Liau Bb

The vast majority of trait-associated genetic variants reside in noncoding cis-regulatory elements (CREs), yet most regulatory sequences remain functionally uncharacterized. CRISPR-based screens enable direct perturbation of CREs in their native genomic context and have expanded into a diverse toolkit, including…

225. From off-target to on-demand: Precision engineering and translational evaluation of next-generation base editors

Wang W, Song J, Du Y, Zhou C, Zuo X, You G, Et Al.

Due to the increasing demand for clinical gene therapy and the limitations of current treatment methods, there is an urgent need to develop gene-editing tools that are safer, more precise, and more clinically implementable. Deaminase-based base editors have emerged as gene-editing platforms with significant…

• Artificial intelligence
• Base editing
• Clinical translation
• Delivery
• Editing efficiency
• Editing precision
• Safety

226. A Scalable, Antibody-Free Lipid Nanoparticle Achieves Preferential mRNA Delivery to Human HSPCs In Vivo Without Conditioning

Kim E, Zenhausern R, Kapadia S, Johnson S, Cho S, Choi J, Et Al.

Systemic nucleic acid delivery to hematopoietic stem and progenitor cells (HSPCs) remains a major barrier to in vivo gene therapy due to hepatic sequestration of lipid nanoparticles (LNPs). Here, we report a scalable, ligand-free HSPC-tropic LNP enabling efficient mRNA delivery to human HSPCs in vivo without…

227. Piperazine-Structured Lipid Nanoparticles Enable Enhanced Targeted Delivery of SHP-1 siRNA to Macrophages for Treatment of Atherosclerotic Vulnerable Plaques

Zhu P, Huang Y, Pan L, Leng Y, Zheng H, Zhou Y, Et Al.

Atherosclerotic vulnerable plaques pose a risk for acute coronary syndrome and sudden cardiac death due to plaque rupture and thrombosis. While nanomedicines modulating macrophage functions have attracted intensive interest, efficient delivery to plaque macrophages remains challenging. Here, mannose-modified lipid…

• SHP-1 siRNA
• lipid nanoparticles
• macrophages
• plaque-targeted delivery
• vulnerable plaques

228. Protein-nanostructure interactions in drug delivery systems: insights from molecular dynamics simulations

Yazdi Ss, Mohammadnejad J, Mehrnejad F

Protein-based therapeutics have become an important part of modern medicine, offering highly specific and effective treatments for a wide range of diseases and improving patients' quality of life compared with many conventional small-molecule drugs. Owing to their macromolecular nature, the successful administration…

• Molecular dynamics simulation
• Nanoparticle
• Protein therapeutics

229. Surface-Functionalized Porphyrinic MOF Nanocarrier with Intrinsic Fluorescence for Enhanced DNA Delivery and Combined Phototherapy

Wang N, Zheng Y, Qi G, Zhou F, Guo C, Xu Y, Et Al.

Multifunctional nonviral gene carriers face the challenge of reconciling efficient DNA condensation, fluorescence traceability, controlled intracellular release, and phototherapeutic activity within a single platform. To address this, we constructed a surface-functionalized porphyrinic metal-organic framework…

230. miR-138-5p: From Multidimensional Tumor-Suppressive Regulatory Networks to Nanocarrier-Based Delivery for Solid Tumor Therapy

Leng T, Lv Y, Ha M, Zhu X, Jiang Y, Hu S, Et Al.

MicroRNA-138-5p (miR-138-5p) has been reported to exert tumor-suppressive effects in several solid tumors, and its downregulation has been associated with malignant progression, therapeutic resistance, and poor prognosis. This review summarizes research trends and current evidence on the molecular functions…

• Exosomes
• Nanocarrier-mediated delivery
• Tumor suppression
• ceRNA
• miR-138-5p

231. RNA-Lipid Interactions Control Structure and Dynamics of Lipid Nanoparticles

Chen X, Xu C, Baiz Cr

Lipid nanoparticles (LNPs) are the leading platform for RNA delivery, enabling applications ranging from mRNA vaccines to CRISPR therapeutics. Ionizable lipids, such as DLin-MC3-DMA (MC3), play a central role in nucleic acid encapsulation and intracellular delivery, yet the molecular mechanisms governing LNP…

232. mRNA-dendritic cell antigen vaccine potentiates CD38 CAR-T Cell therapy for relapsed/refractory acute myeloid leukemia

Lu Y, Cai X, Li Y, Lv Y, Tang Y, Li Y, Et Al.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising strategy for management of relapsed/refractory acute myeloid leukemia (R/R AML). Safety and preliminary activity of CD38-targeted CAR-T cells in R/R AML were demonstrated in our prior study; however, relapse with CD38-positive blasts persisted…

• CD38
• acute myeloid leukemia
• antigen-presenting cell
• chimeric antigen receptor T cell
• lipid nanoparticle
• mRNA vaccine

233. Rationally designed negatively charged lipid nanoparticles reduce systemic reactogenicity of mRNA vaccines while preserving immunogenicity

Karaki T, Inoue W, Gis T, Shichinohe S, Watanabe T, Hirai T, Et Al.

Messenger RNA (mRNA) vaccines have emerged as versatile platforms for the prevention of infectious diseases and therapeutic cancer vaccination. However, strong reactogenicity remains a key challenge, with severe adverse events such as myocarditis. These concerns may limit the applications of mRNA vaccines. As lipid…

• Adverse reactions
• Anionic phospholipids
• Biodistribution
• Lipid nanoparticles
• Negatively charged LNPs
• Reactogenicity
• mRNA vaccines

234. Serotype-Tailored Midstream and Downstream Operations to Advance the Manufacturing of Adeno-Associated Viral Vectors

Minzoni A, Shastry S, Barbieri E, Hurst Mr, Idanwekhai K, Wu Y, Et Al.

Adeno-associated viruses (AAVs) are the leading vectors for in vivo gene therapy, fueling a growing demand for scalable and robust biomanufacturing processes. Yet, the impact of cell lysis conditions on the performance of midstream and downstream unit operations across serotypes remains poorly characterized. This…

• Bayesian optimization
• adeno‐associated virus
• midstream
• purification
• upstream

235. A Combinatorial mRNA Therapy for Treating Rheumatoid Arthritis and Osteoarthritis by Inhibiting Inflammation and Preventing Cartilage Degeneration

Wang G, Guo Y, Guo K, Zhang C, Zhou Y, Xia J, Et Al.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are debilitating joint disorders with distinct etiologies but share common pathological features of chronic inflammation and progressive cartilage damage. Current therapeutic options are largely palliative and yet fail to achieve desired effect. In this study, we…

236. Circular RNA Delivery In Vitro and In Vivo Using Doubly Branched Aminoethoxy-Functionalized Ionizable Lipid Nanoparticles

Cook A, Yadav Pk, Helmy Ew, Vlasova K, Chang Hy, Wender Pa

Circular RNA is a therapeutically promising RNA modality with superior stability and extended protein expression relative to linear RNA. While delivery systems for linear RNA have received much attention, less effort has been directed toward the delivery of circular RNA, whose closed topology and physicochemical…

237. Targeted Gastrointestinal Delivery of mRNA Lipid Nanoparticles Enables Systemic Vaccination and Glucagon-like Peptide-1 Metabolic Therapy

Abbas Am, Ghanim R, Rudden S, Schultz D, Jang B, Shakked A, Et Al.

Lipid nanoparticles (LNPs) administered parenterally often show poor localization to multiple tissue types, including the pancreas and gastrointestinal (GI) tract. Furthermore, patients typically prefer orally administered drugs to those that are given parenterally. We therefore investigated whether GI LNP…

• GLP-1 mRNA
• Gastrointestinal delivery
• Lipid nanoparticles
• Oral delivery
• Pancreatic delivery
• Vaccine
• mRNA delivery

238. Lipid Nanoparticles at the Crossroads of Chemistry and Medicine: A Tutorial

Rogado Mt, Wang A, Zeng S, Wang Z, Burda C

Lipid nanoparticles (LNPs) have risen to the forefront of modern therapeutics by enabling the clinical success of COVID-19 mRNA vaccines. In order for them to function as drug delivery vesicles, LNPs must have scalable, tunable, and targeted nanoscale platforms whose strengths in versatility, performance, and…

• cellular uptake
• endosomal escape
• gene therapy
• lipid nanoparticles (LNPs)
• nanoparticles
• nanoplatform technology
• payload encapsulation
• targeted drug delivery

239. Osteoporosis treatment via programmed delivery of IRF5 siRNA to macrophages in bone tissue combined with ROS scavenging

Chen Z, Wu J, Zhu Y, Tan A, Deng J, Niu Y, Et Al.

Postmenopausal osteoporosis (PO) is not merely a consequence of increased osteoclast activity. Estrogen deficiency induces oxidative stress and pro-inflammatory M1 macrophage polarization in bone tissue, thereby sustaining osteoclastogenic stimuli and pathological bone resorption. Interferon regulatory factor 5…

• Macrophage polarization
• Platinum nanozyme
• Postmenopausal osteoporosis
• ROS-Responsive nanotherapeutics

240. Impact of the protein corona in RGD-functionalized nanoliposomes delivering enzymatic replacement therapy for Fabry disease

Moltó-Abad M, Tomsen-Melero J, Villagrasa-Araya V, Marijuan-Pinel D, Díaz-Riascos Zv, Canals F, Et Al.

The protein corona (PC) formed upon nanoparticle exposure to blood critically defines their biological identity and in vivo fate, yet its impact on targeted liposomal enzyme replacement therapies (ERTs) remains incompletely understood. Here, we systematically investigated how RGD functionalization (including varying…

• Enzyme replacement therapy
• Fabry disease
• Nanoliposomes
• Protein corona
• RGD
• biodistribution