A5052600113- Genetic Neurodegenerative Diseases
- Retinal Development and Disorders
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
- Retinal and Macular Surgery
- Neuroscience and Neural Engineering
- Virus-based gene therapy research
- Reproductive Biology and Fertility
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Retinal Diseases and Treatments
- RNA Interference and Gene Delivery
- DNA Repair Mechanisms
- Neurological disorders and treatments
- Animal Behavior and Welfare Studies
- Biochemical effects in animals
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Advanced Drug Delivery Systems
- Biotin and Related Studies
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Muscle activation and electromyography studies
- Bee Products Chemical Analysis
Czech Academy of Sciences, Institute of Animal Physiology and Genetics
2016-2025
University of Edinburgh
2023
Oslo University Hospital
2022
University of Oslo
2022
Czech Academy of Sciences
2004-2021
Institute of Animal Physiology of the Slovak Academy of Sciences
2021
Discovery Institute
2019
Sanford Burnham Prebys Medical Discovery Institute
2014-2019
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the huntingtin gene. Previously, we showed strong reduction and prevention of neuronal dysfunction HD rodents using an engineered microRNA targeting human huntingtin, delivered via adeno-associated virus (AAV) serotype 5 vector with transgene encoding miRNA against HTT mRNA (AAV5-miHTT). One challenges as model diseases their relatively small brain, making successful translation to...
Abstract Clustered regularly interspaced short palindromic repeats-associated protein (CRISPR/Cas9) system has become a revolutionary tool for gene editing. Since viral delivery systems have significant side effects, and naked DNA is not an option, the nontoxic, non-viral of CRISPR/Cas9 components would significantly improve future therapeutic delivery. In this study, we aim at characterizing nanoparticles to deliver plasmid encoding CRISPR-Cas in eukaryotic cells vitro . complexed...
Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is a progressive neurodegenerative disorder caused by CAG expansion in the ATXN3 gene. The expanded repeat translated into prolonged polyglutamine ataxin-3 protein and accumulates within inclusions, acquiring toxic properties, which results degeneration of cerebellum brain stem. In current study, non-allele-specific silencing approach was investigated using artificial microRNAs engineered to target various regions gene...
Striatal delivery of microRNA-gene therapy results in widespread brain huntingtin protein lowering Huntington’s disease minipigs up to 1 year.
In vitro maturation (IVM) of fully grown mammalian oocytes is characterized by initial germinal vesicle (GV) breakdown and rearrangement microtubule network during the first meiosis (MI), followed extrusion polar body block in metaphase second (MII). Only matured are capable undergoing fertilization initiation zygotic development. These observations mostly based on morphological evaluation; however, molecular events responsible for these processes not known. this study, we have launched...
Aims/Purpose: The study of long‐term survival transplanted retinal pigment epithelium (RPE) in animal models is very important for the development promising cell‐based therapy degenerative diseases such as age‐related macular degeneration (AMD) or retinitis pigmentosa. We hereby present xenogeneic implantation human iPSC‐RPEs into minipig eyes with a 6‐week follow‐up period. Methods: subretinal implantations hiPSC‐RPEs‐scaffolds were performed using 3‐port pars plana vitrectomy. character...
Purpose: This study aimed to evaluate early-phase safety of subretinal application AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects a vehicle control, low dose, and high dose. Methods: Twelve WT pigs (24 eyes) were divided into three groups: four each received bilateral injections either vehicle, dose (3.3 × 1010 vector genomes [vg] per eye), or (1.0 1011 vg eye). Total retinal thickness (TRT) was evaluated using optical coherence tomography function assessed...
In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age-related macular degeneration (AMD), loss pigment epithelia (RPE) cells subsequently photoreceptors in the area result a dramatic decline central visual function. Repopulating this with functional RPE may prevent progression photoreceptor loss. present study, viability, survival, integration human induced pluripotent stem cell (hiPSC)-derived (hiPSC-RPE) is assessed generated using...
Glycation of proteins is often considered as a method to improve their functional properties for promising applications in wound healing. Furthermore, marked increase percentage radical scavenging activity the conjugates makes it an effective antioxidant synthetic strategy. A simple conjugation process was employed develop bovine serum albumin-dextran (BSA-dextran) using Maillard reaction. Higher electrophoretic mobility and surface charge prepared observed native PAGE electrophoresis zeta...
In this study, we performed proteomic analysis of porcine oocytes during in vitro maturation. Comparison at the initial and final stages meiotic division characterized candidate proteins that were differentially synthesized While biosynthesis many these was significantly decreased, found four with increased biosynthetic rate, which are supposed to play an essential role meiosis. Among them, ubiquitin C-terminal hydrolase-L1 (UCH-L1) identified by mass spectrometry. To study regulatory UCH-L1...
<b><i>Background:</i></b> Huntington's disease is induced by CAG expansion in a single gene coding the huntingtin protein. The mutated (mtHtt) primarily causes degeneration of neurons brain, but it also affects peripheral tissues, including testes. <b><i>Objective:</i></b> We studied sperm and testes transgenic boars expressing N-terminal region human mtHtt. <b><i>Methods:</i></b> In this study, measures reproductive...
Recently developed therapeutic approaches for the treatment of Huntington's disease (HD) require preclinical testing in large animal models. The minipig is a suitable experimental because its gyrencephalic brain, body weight 70-100 kg, long lifespan, and anatomical, physiological metabolic resemblance to humans. Libechov transgenic model HD (TgHD) has proven useful proof concept developing new therapies. However, evaluate efficacy different therapies on progression, broader phenotypic...
The development of primary human retinal pigmented epithelium (hRPE) for clinical transplantation purposes on biodegradable scaffolds is indispensable. We hereby report the results subretinal implantation hRPE cells nanofibrous membranes in minipigs.The hRPEs were collected from cadaver donor eyes and cultivated ultrathin carriers prepared via electrospinning poly(L-lactide-co-DL-lactide) (PDLLA). "Libechov" minipigs (12-36 months old) used study, supported by preoperative tacrolimus...
Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement dysfunctional human retinal pigment epithelium (hRPE) cells by transplantation vitro-cultivated hRPE to affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise powerful cell carriers, but biodegradability requirement, it also poses challenge due its limited durability. exhibit several characteristics that putatively respond...
ABSTRACT Skeletal muscle wasting and atrophy is one of the more severe clinical impairments resulting from progression Huntington's disease (HD). Mitochondrial dysfunction may play a significant role in etiology HD, but specific condition mitochondria has not been widely studied during development HD. To determine skeletal early stages we analyzed quadriceps femoris 24-, 36-, 48- 66-month-old transgenic minipigs that expressed N-terminal portion mutated human huntingtin protein (TgHD)...
Huntington's disease (HD) is an autosomal dominant affecting neurons predominantly in the striatum due to production of toxic huntingtin protein. Lowering concentration mutant a promising therapeutic approach, and suitable delivery system fascinating. Nanoparticles (NPs) minimize host immune response have no limit concerning number NPs administered. They are safe, targeted, effective for RNA therapeutics providing significant mode cross blood–brain barrier broad range clinical applications....
Purpose To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model.
In this study, we document that the overall rate of protein synthesis decreases during in vitro maturation (IVM) pig oocytes despite enhanced formation 5' cap structure eIF4F. Within somatic/interphase cells, eIF4F complex correlates very well with rates translation, and is controlled primarily by availability binding eIF4E. We show eIF4E inhibitory protein, 4E-BP1, becomes phosphorylated IVM, which results gradual release from as documented immunoprecipitation analyses. Isoelectric focusing...
Eukaryotic initiation factor 4E (eIF4E) plays an important role in mRNA translation by binding the 5'-cap structure of and facilitating recruitment to other factors 40S ribosomal subunit. eIF4E undergoes regulated phosphorylation on Ser-209 this is believed be for its factors. The findings showing that becomes gradually phosphorylated during vitro maturation (IVM) pig oocytes with a maximum metaphase II (M II) stage have been documented us recently (Ellederova et al., 2006). aim work was...
<b><i>Background:</i></b> Huntington disease (HD) is an incurable neurodegenerative caused by the expansion of a polyglutamine sequence in gene encoding huntingtin (Htt) protein, which expressed almost all cells body. In addition to small animal models, new therapeutic approaches (including therapy) require large models as their brains are more realistic model for translational research. <b><i>Objective:</i></b> this study, we describe...
ABSTRACT Huntington's disease (HD) is a monogenic, progressive, neurodegenerative disorder with currently no available treatment. The Libechov transgenic minipig model for HD (TgHD) displays neuroanatomical similarities to humans and exhibits slow progression, therefore more powerful than mouse models the development of therapy. phenotypic characterization this still ongoing, it essential validate biomarkers monitor progression intervention. In study, behavioral phenotype (cognitive, motor...