Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Non-viral gene delivery systems are being developed to address limitations of viral gene delivery. Many of these non-viral systems are modeled on the properties of viruses including cell surface binding, endocytosis, endosomal escape, and nuclear targeting. Most non-viral gene transfer systems exhibit little correlation between in vitro and in vivo efficiency, hampering a systematic approach to their development. Previously, we have described a 3.5 kDa peptide (peptide for ocular delivery [POD]) that targets cell surface sialic acid. When functionalized with polyethylene glycol (PEG) via a sulfhydryl group on the N-terminal cysteine of POD, PEG-POD could compact plasmid DNA, forming 120- to 180-nm homogeneous nanoparticles. PEG-POD enabled modest gene transfer and rescue of retinal degeneration in vivo. Systematic investigation of different stages of gene transfer by PEG-POD nanoparticles was hampered by their inability to deliver genes in vitro. Herein, we describe functionalization of POD with PEG using a reducible orthopyridyl disulfide bond. These reducible nanoparticles enabled gene transfer in vitro while retaining their in vivo gene transfer properties. These reducible PEG-POD nanoparticles were utilized to deliver human FLT1 to the retina in vivo, achieving a 50% reduction in choroidal neovascularization in a murine model of age-related macular degeneration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491761 | PMC |
| http://dx.doi.org/10.1016/j.omtn.2017.06.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
AAV-mediated delivery of a broadly neutralizing anti-flavivirus antibody protects against dengue and Zika viruses in a mouse model.
Mol Ther
September 2025
Institute of Biomedical Sciences, Academia Sinica, Taipei 115201, Taiwan,; Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 114201, Taiwan, ; Biomedical Translation Research Center, Academia Sinica, Taipei 115201, Taiwan,. Electronic address:
Flaviviruses contain many important human pathogens such as dengue virus (DENV) and Zika virus (ZIKV), for which effective and safe vaccines are still lacking, mainly because pre-existing cross-reactive non-neutralizing antibodies may exacerbate subsequent infections with related flaviviruses. To overcome this challenge, we explore Vectored ImmunoProphylaxis (VIP), which involves the passive transfer of protective antibody genes via viral vectors for in vivo expression. We utilized a recombinant adeno-associated virus (rAAV) to express a broad anti-flavivirus neutralizing human monoclonal antibody, bnAb 752-2C8, and tested its protection against four serotypes of DENV and ZIKV.
View Article and Find Full Text PDFThe impact of melatonin-enriched media on epigenetic and perinatal changes induced by embryo culture in a mouse model.
J Assist Reprod Genet
September 2025
Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
Purpose: To determine if melatonin-enriched culture media could offset loss of imprinting in mouse concepti.
Methods: Zygotes were cultured to blastocyst stage under optimized conditions in melatonin-supplemented media at either 10 M (MT 10) or 10 M (MT 10), or without supplementation (Culture + embryo transfer, or ET, positive control). Blastocysts were also developed in vivo (ET negative control).
Can Sex-based Variations in the Immune Responses to AAV Gene Therapy Affect Safety and Efficacy? A Review of Current Understanding.
AAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFAutophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.
Mol Psychiatry
September 2025
Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, 44115, USA.
Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.
View Article and Find Full Text PDFIntegration of in vivo stress reporters with transcription profiling to define chemical mixtures mechanisms of toxicity, including trans-generational effects.
Chem Biol Interact
September 2025
Department of Systems Medicine. School of Medicine. University of Dundee, Ninewells Hospital, Dundee, DD1 9SY, UK.
Humans are exposed to mixtures of chemical pollutants from various environmental sources at all stages of life. Understanding how these compounds are causally linked to population health effects is challenging because of the ethical limitations on studying controlled human exposures and the complexity of the many potential molecular mechanisms involved. We hypothesized that studies using a combination of in vivo murine stress reporter models together with non-targeted global transcriptome analysis will define the toxic mechanisms of complex chemical mixtures in a physiological context.
View Article and Find Full Text PDF