Peptide-Functionalized Lipid Nanoparticles for Targeted Systemic mRNA Delivery to the Brain

Nano Letters, Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due blood-brain barrier (BBB) and tendency vehicles accumulate liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA brain. We utilize click chemistry functionalize LNPs with peptides that target receptors overexpressed on endothelial cells neurons, namely RVG29, T7, AP2, mApoE peptides. evaluate effect LNP targeting neuronal cell transfection vitro, investigating factors serum protein adsorption, intracellular trafficking, transcytosis, exosome secretion. Finally, show peptide functionalization enhances mouse reduces hepatic after systemic administration. Specifically, RVG29 improved vivo, establishing its potential nonviral delivering

Язык: Английский

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Gene therapies for neurogenetic disorders

Trends in Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Interaction design in mRNA delivery systems

Journal of Controlled Release, Год журнала: 2024, Номер 377, С. 413 - 426

Опубликована: Ноя. 26, 2024

Язык: Английский

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Gene therapy for sickle cell disease and thalassemia

Current Opinion in Hematology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Purpose of review Thalassemia and sickle cell disease are among the most frequent monogenic hereditary diseases. Access to transfusions, iron chelation therapies drugs such as hydroxyurea have improved life expectancy quality life. However, these diseases still cause significant disability. The first available curative therapy, bone marrow transplantation, is unfortunately not feasible for all patients. Over past decade, numerous studies focused on finding new therapies, many clinical trials evaluated different gene therapy approaches. Recent findings therapeutic targets focus adding functional copies encoding β-globin in defective CD34 + cells, mainly using lentiviral vectors directed towards HSCs. More recently, has shifted inducing fetal hemoglobin production at levels or repairing underlying molecular defect, novel editing techniques involving CRISPR-Cas9, transcription activation-like effector protein nucleases, zinc finger nucleases base editing. Preclinical now optimizing how performed delivered reduce eliminate myeloablative treatment its potential adverse events. Summary In this review, we explore induce repair defect that causes genetically. Here, recent opening a era hemoglobinopathies.

Язык: Английский

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Investigation of the Protein Corona and Biodistribution Profile of Polymeric Nanoparticles for Intra-Amniotic Delivery

Biomaterials, Год журнала: 2025, Номер 320, С. 123238 - 123238

Опубликована: Март 6, 2025

Язык: Английский

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Modular Layer-by-Layer Nanoparticle Platform for Hematopoietic Progenitor and Stem Cell Targeting

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Effective delivery of drug and gene cargos to hematopoietic stem progenitor cells (HSPCs) is a major challenge. Current therapeutic strategies in genetic disorders or hematological malignancies are hindered by high costs, low accessibility, off-target toxicities. Layer-by-layer nanoparticles (LbL NPs) modular systems with tunable surface properties enable highly specific targeting. In this work, we developed LbL NPs that target HSPCs via antibody functionalization reduced uptake circulating myeloid cells. layered poly(acrylic acid), bioinert polymer, provided more stealth vivo than other tested bioactive polyanions. The additional conjugation anti-cKit anti-CD90 antibodies improved NP 2- 3-fold nondifferentiated bone marrow vitro. By contrast, anti-CD105 functionalized showed the highest association vivo, ranging from 3.0 8.5% subpopulations. This platform was then adapted human HSPC receptors, similar targeting trends healthy CD34+ anti-CXCR4 demonstrated greatest B-cell lymphoma leukemia Taken together, these results underscore potential capacity disease-dependent context.

Язык: Английский

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In Utero Therapies, the Next Frontier

American Journal of Medical Genetics Part C Seminars in Medical Genetics, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

ABSTRACT Advancements in molecular diagnostics and the expanded understanding of pathophysiologic processes underlying a variety genetic conditions have led to design implementation many targeted therapies past decade. In prenatal space, these advancements rapidly changed field diagnosis garnered enthusiasm toward interventions aimed at correcting specific disease mechanisms utero prevent irreversible injury and/or leverage fetal physiology increase effectiveness treatments. Although promising trials are underway, continued efforts fully elucidate intricacies immunology, blood–brain barrier precise during different stages development will be paramount refinement therapies. The social ethical implications therapy also utmost importance, especially an era increasing restrictions on reproductive autonomy. This review aims summarize current as well history such endeavors.

Язык: Английский

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Circular RNAs modulate cancer drug resistance: advances and challenges

Cancer Drug Resistance, Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Acquired drug resistance is a main factor contributing to cancer therapy failure and high mortality, highlighting the necessity develop novel intervention targets. Circular RNAs (circRNAs), an abundant class of RNA molecules with closed loop structure, possess characteristics including stability, which provide unique advantages in clinical application. Growing evidence indicates that aberrantly expressed circRNAs are associated against various treatments, targeted therapy, chemotherapy, radiotherapy, immunotherapy. Therefore, targeting these aberrant may offer strategy improve efficiency therapy. Herein, we present summary most recently studied their regulatory roles on resistance. With advances artificial intelligence (AI)-based bioinformatics algorithms, could emerge as promising biomarkers targets

Язык: Английский

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Integration of Clinical, Radiographic, Histologic, and Molecular Findings to Diagnose Craniofacial Fibrous Dysplasia

Journal of Craniofacial Surgery, Год журнала: 2025, Номер unknown

Опубликована: Апрель 28, 2025

Fibrous dysplasia (FD) is a benign bone tumor consisting of fibrotic deposits interwoven with disorganized bone. Craniofacial FD characterized by progressive expansile overgrowth resulting in facial disfigurement, vision loss, jaw disfunction, and pain. Diagnosis often made clinical presentation suggestive radiographic findings, histologic genetic analyses recommended questionable cases. However, testing the lesions can lead to false negatives, as contain both normal neoplastic cells. To explore concordance between diagnostic tools, we evaluated history, imaging, histology, 6 Six subjects presented abnormal bony imaging FD. Histologic examination excised revealed 4 cases pathologic findings consistent FD, 1 case diagnosed juvenile psammomatoid ossifying fibroma (JPOF), vascular malformation. Given that somatic mosaicism underpins pathogenesis, targeted sequencing GNAS gene was performed from different tissue sources, including blood, lesion, primary cell culture. pathogenic variants were detected lesion all cases, demonstrating JPOF features. The authors found mutational burden cells containing variant ranges 35.8% 46.8% 31.0% 49.7% cultured stromal variable correlation radiographic, histologic, molecular diagnosis this study highlights heterogeneity challenges accurate diagnosis. By culturing cells, provide source material for future experiments.

Язык: Английский

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In utero lipid nanoparticle delivery achieves robust editing in hematopoietic stem cells.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 12, 2025

In vivo genome editing for hematologic malignancies is limited by inefficient delivery of editors to hematopoietic stem cells (HSC) in the bone marrow. To overcome this limitation, we capitalized on inherent liver tropism lipid nanoparticles (LNPs) and niche fetal HSCs. We demonstrate that utero LNPs without active targeting ligands results potentially therapeutic levels HSC editing.

Язык: Английский

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