Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we have developed an mRNA therapeutic for the lower lung using one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a delivery vehicle. We deliver an anti-inflammatory cytokine mRNA, transforming growth factor-beta (TGF-β), to produce transient protein expression in the lower regions of the lung. This study highlights IAJD's potential for precise, effective, and safe delivery of TGF-β mRNA to the lung. This delivery system offers a promising approach for targeting therapeutics to the specific tissues, a strategy necessary to fill the current clinical gap in treating parenchymal lung injury and disease.
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http://dx.doi.org/10.21203/rs.3.rs-4656663/v1 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Innovative Genomics Institute, University of California, Berkeley, CA 94720.
The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.
View Article and Find Full Text PDFPLoS One
January 2025
Women and Health Initiative, Department of Global Health and Population, Harvard University T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
In 2015, the World Health Organization (WHO) released global targets and strategies for reducing maternal mortality in the Sustainable Development Goal (SDG) period developed through broad stakeholder consultations. The targets and strategies identified in the "Strategies toward Ending Preventable Maternal Mortality (EPMM)" report are grounded in a systemic and human rights approach to maternal health and aim to address the broad spectrum of key social, political, economic, and health system determinants of maternal health and survival, as exemplified by 11 Key Themes. These upstream determinants of maternal survival are not well represented in maternal health measurement efforts, which tend to focus on service delivery.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
To bolster the capacity for managing potential infectious diseases in the future, it is critical to develop specific antiviral drugs that can be rapidly designed and delivered precisely. Herein, a CRISPR/Cas13d system for broad-spectrum targeting of influenza A virus (IAV) from human, avian, and swine sources is designed, incorporating Cas13d mRNA and a tandem CRISPR RNA (crRNA) specific for the highly conserved regions of viral polymerase acidic (PA), nucleoprotein (NP), and matrix (M) gene segments, respectively. Given that the virus targets cells with specific receptors but is not limited to a single organ, a Susceptible Cell Selective Delivery (SCSD) system is developed by modifying a lipid nanoparticle with a peptide mimicking the function of the hemagglutinin of influenza virus to target sialic acid receptors.
View Article and Find Full Text PDFJ ECT
December 2024
From the Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy.
Autoimmune encephalitis (AE) tends to manifest as a mixture of neuropsychiatric and somatic symptoms, either of which may predominate, and often shows a progressive clinical course sometimes leading to life-threatening conditions. Catatonic and psychotic syndromes, regardless of whether associated with dysautonomia, are common manifestations of AE, especially concerning the anti-NMDAR subtype. Several autoantibodies targeting different neuronal epitopes have been linked to specific clinical manifestations and their detection is embedded in some of the diagnostic criteria for AE.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, 450001, China.
Although cytotoxic T lymphocytes (CTLs) activation combined with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade have emerged as an effective strategy to improve immunotherapeutic potency, it remains challenging to realize the spatiotemporal synergy of these two components. Herein, the study reports an engineered bacterial-based delivery system that can simultaneously promote CTLs infiltration and control PD-L1 binding protein (PD-L1 trap) release on demand at tumor site. The drug release button of this tumor targeting system is the specific temperature, which is accomplished by dual-modified melanin nanoparticles with photothermal conversion capacity on the engineered bacterial.
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