A5052185926- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- CAR-T cell therapy research
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Virus-based gene therapy research
- Advanced biosensing and bioanalysis techniques
- 3D Printing in Biomedical Research
- Hemophilia Treatment and Research
- Thyroid Disorders and Treatments
- RNA Interference and Gene Delivery
- Congenital heart defects research
- Image Processing and 3D Reconstruction
- Muscle Physiology and Disorders
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Amyotrophic Lateral Sclerosis Research
- Blood Coagulation and Thrombosis Mechanisms
- Eosinophilic Disorders and Syndromes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- 3D Surveying and Cultural Heritage
- Trypanosoma species research and implications
- Cell Adhesion Molecules Research
- Congenital Anomalies and Fetal Surgery
- Innovation and Socioeconomic Development
Central South University
2016-2024
University of South China
2024
Spinal muscular atrophy (SMA) is a kind of neuromuscular disease characterized by progressive motor neuron loss in the spinal cord. It caused mutations survival 1 (SMN1) gene. SMN1 has paralogous gene, 2 (SMN2), humans that present almost all SMA patients. The generation and genetic correction patient-specific induced pluripotent stem cells (iPSCs) viable, autologous therapeutic strategy for disease. Here, c-Myc-free non-integrating iPSCs were generated from urine an patient using episomal...
Abstract Mesenchymal stem cells (MSCs) are a promising cellular vehicle for transferring anti-cancer factors to malignant tumors. Currently, variety of agents, including the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), have been loaded into MSCs derived from range sources through different engineering methods. These engineered exhibit enormous therapeutic potential various cancers. To avoid intrinsic defects tissues and risk viral vectors, TRAIL was...
Spinal muscular atrophy (SMA) is a devastating autosomal recessive motor neuron disease associated with mutations in the survival 1 (SMN1) gene, leading genetic cause of infant mortality. A nearly identical copy gene (SMN2) retained almost all patients SMA. However, SMN2 fails to prevent development because its alternative splicing, lack exon 7 majority transcripts and yielding an unstable truncated protein. Several splicing regulatory elements, including intronic silencer-N1 (ISS-N1) have...
Given that the cDNA of F8 is too large to be packaged into adeno-associated virus (AAV) capsids, gene transfer some versions B-domain-deleted (BDD-F8) for hemophilia A (HA) treatment has been attempted with promising results. Here, we describe an efficient correction via single-stranded-oligodeoxynucleotide (ssODN)-mediated in-frame deletion within B domain CRISPR/Cas9 in HA-patient-derived induced pluripotent stem cells (HA-iPSCs). The expression and activity FVIII was restored corrected...
Introduction: Hemophilia A (HA) is the most common genetic bleeding disorder caused by mutations in F8 gene encoding coagulation factor VIII (FVIII). As second predominant pathogenic mutation hemophilia severe patients, Intron one inversion (Inv1) completely splits into two parts and disrupts transcription, resulting no FVIII protein production. The part which contains exon 2-exon 26 covers 98% of coding region. Methods: We hypothesized that situ manipulation to add a promoter before could...
Abstract Aims The ubiquilin‐like protein ubiquilin 2 (UBQLN2) is associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). biological function of UBQLN2 has previously been shown to be related stress granules (SGs). In this study, we aimed clarify the regulatory relationship between SGs. Methods transfected UBQLN2‐WT or UBQLN2‐P497H plasmids into cell lines (HEK293T, HeLa), observed process SG dynamics by immunofluorescence. Meanwhile, immunoblot analyses...
Induced pluripotent stem cells (iPSCs) are a promising source of mesenchymal (MSCs) for clinical applications. In this study, we transformed human iPSCs using non-viral vector carrying the IL24 transgene pHrn-IL24. PCR and southern blotting confirmed integration into rDNA loci in four 68 iPSC clones. We then differentiated high expressing IL24-iPSC clone MSCs (IL24-iMSCs) that showed higher expression culture supernatants cell lysates than control iMSCs. IL24-iMSCs efficiently osteoblasts,...
Hemophilia B (HB) is an X-linked recessive bleeding disorder, caused by F9 gene deficiency. Gene therapy combined with the CRISPR/Cas9 technology offers a potential cure for hemophilia B. Now Cas9 nickase (Cas9n) shows great advantage in reducing off-target effect compared wild-type Cas9. In this study, we found that multicopy ribosomal DNA (rDNA) locus, homology directed recombination (HDR) efficiency induced sgRNA-Cas9n was much higher than sgRNA-Cas9, meanwhile without six predicted...
The JAK2 V617F mutation is a major diagnostic, therapeutic, and monitoring molecular target of Philadelphia-negative myeloproliferative neoplasms (MPNs). To date, numerous methods detecting the have been reported, but there no gold-standard diagnostic method for clinical applications. Here, we developed validated an efficient Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein 12a (Cas12a)-based assay to detect mutation. Our results showed that...
Hemophilia A (HA) is a common X-linked recessive hereditary bleeding disorder. Coagulation factor VIII (FVIII) insufficient in patients with HA due to the mutations F8 gene. The restoration of plasma levels FVIII via both recombinant B-domain-deleted (BDD-FVIII) and (BDDF8) transgenes was proven be helpful. FVIII-Padua 23.4 kb tandem repeat mutation associated high gene expression thrombogenesis. Here we screened core enhancer element for improving expression. In detail, identified 400 bp...
Hemophilia B (HB) is an X-linked recessive disease caused by F9 gene mutation and functional coagulation factor IX (FIX) deficiency. Patients suffer from chronic arthritis death threats owing to excessive bleeding. Compared with traditional treatments, therapy for HB has obvious advantages, especially when the hyperactive FIX mutant (FIX-Padua) used. However, mechanism which FIX-Padua works remains ambiguous due a lack of research models. Here, in situ introduction F9-Padua was performed...
Spinal muscular atrophy (SMA) is characterized by severe lethality and irreversible progression. Early diagnosis of SMA more practical significance with the emergence effective therapy. However, existing techniques to identify patients rely on cumbersome instruments, hindering their accessibility application. An SMA-Cas12a-strip assay was developed integration Cas12a-based nucleic acid detection, isothermal amplification, lateral flow strip. The analytical performance assessed clinical...
Duchenne muscular dystrophy (DMD) is the most common fatal muscle disease, with an estimated incidence of 1/3500–1/5000 male births, and it associated mutations in X-linked DMD gene encoding dystrophin, largest known human gene. There currently no cure for DMD. The large size hampers exogenous addition delivery. genetic correction patient-derived induced pluripotent stem cells (DMD-iPSCs) differentiation into suitable transplantation a promising autologous therapeutic strategy In this study,...
Primary congenital hypothyroidism (CH) is a common neonatal endocrine disorder characterized by elevated concentrations of thyroid stimulating hormone (TSH) and low free thyroxine (FT4). PAX8 NKX2-1 are important transcription factors involved in development. In this study, we detected three novel variants (c.149A > C c.329G A) (c.706A G) whole exome sequencing (WES) unrelated CH patients with variable phenotypes. The results Western blot immunofluorescence analysis showed that the had no...
Hemophilia A (HA), an X-linked recessive congenital bleeding disorder, affects 80%–85% of patients with hemophilia. Nearly half severe cases hemophilia are caused by a 0.6-Mb genomic inversion (Inv22) that disrupts F8 . Although viral-based gene therapy has shown therapeutic effects for B (HB), this promising approach is not applicable HA at the present stage; limitation mainly due to large size cDNA, which far exceeds adeno-associated virus (AAV) packaging capacity. We previously reported...
Hemophilia A (HA) is caused by mutations in the coagulation factor VIII (FVIII) gene (F8). Gene therapy a hopeful cure for HA; however, FVIII inhibitors formation hinders its clinical application. Given that platelets promote via locally releasing α-granule, ectopically expressed has been attempted, with promising results HA treatment. The B-domain-deleted F8 (BDDF8), driven truncated ITGA2B promoter, was targeted at ribosomal DNA (rDNA) locus of patient-specific induced pluripotent stem...