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  1. Article ; Online: The key piece of the airway remodeling puzzle revealed—LIGHT signaling in the lung

    Ziyan Rachel Chen / Jim Hu

    Genes and Diseases, Vol 10, Iss 4, Pp 1131-

    2023  Volume 1132

    Keywords Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher KeAi Communications Co., Ltd.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy

    Ranmal Avinash Bandara / Ziyan Rachel Chen / Jim Hu

    Cell & Bioscience, Vol 11, Iss 1, Pp 1-

    2021  Volume 9

    Abstract: Abstract Since CRISPR/Cas9 was harnessed to edit DNA, the field of gene therapy has witnessed great advances in gene editing. New avenues were created for the treatment of diseases such as Cystic Fibrosis (CF). CF is caused by mutations in the Cystic ... ...

    Abstract Abstract Since CRISPR/Cas9 was harnessed to edit DNA, the field of gene therapy has witnessed great advances in gene editing. New avenues were created for the treatment of diseases such as Cystic Fibrosis (CF). CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Despite the success of gene editing with the CRISPR/Cas9 in vitro, challenges still exist when using CRISPR/Cas9 in vivo to cure CF lung disease. The delivery of CRISPR/Cas9 into lungs, as well as the difficulty to achieve the efficiency required for clinical efficacy, has brought forth new challenges. Viral and non-viral vectors have been shown to deliver DNA successfully in vivo, but the sustained expression of CFTR was not adequate. Before the introduction of Helper-Dependent Adenoviral vectors (HD-Ad), clinical trials of treating pulmonary genetic diseases with first-generation viral vectors have shown limited efficacy. With the advantages of larger capacity and lower immunogenicity of HD-Ad, together with the versatility of the CRISPR/Cas9 system, delivering CRISPR/Cas9 to the airway with HD-Ad for lung gene therapy shows great potential. In this review, we discuss the status of the application of CRISPR/Cas9 in CF gene therapy, the existing challenges in the field, as well as new hurdles introduced by the presence of CRISPR/Cas9 in the lungs. Through the analysis of these challenges, we present the potential of CRISPR/Cas9-mediated lung gene therapy using HD-Ad vectors with Cystic Fibrosis lung disease as a model of therapy.
    Keywords Adenovirus ; Gene therapy ; Airway gene delivery ; Cas9 ; Cystic fibrosis ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
    Subject code 610
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: iPSC-based treatment of age-related macular degeneration (AMD)

    Fei Li / Jim Hu / Tong-Chuan He

    Genes and Diseases, Vol 4, Iss 2, Pp 41-

    The path to success requires more than blind faith

    2017  Volume 42

    Abstract: Induced pluripotent stem cells (iPSCs) hold great promise for the treatment of human diseases. Two recent first-of-its-kind clinical case reports on the iPSC-based treatment of age-related macular degeneration (AMD) highlight the hopes and challenges ... ...

    Abstract Induced pluripotent stem cells (iPSCs) hold great promise for the treatment of human diseases. Two recent first-of-its-kind clinical case reports on the iPSC-based treatment of age-related macular degeneration (AMD) highlight the hopes and challenges associated with the clinical application of iPSCs.
    Keywords Autologous iPSC ; Human ; Macular degeneration ; Retinal pigment epithelium ; Transplantation ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Language English
    Publishing date 2017-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Gene therapy for cystic fibrosis

    Jin-A Lee / Alex Cho / Elena N. Huang / Yiming Xu / Henry Quach / Jim Hu / Amy P. Wong

    Journal of Translational Medicine, Vol 19, Iss 1, Pp 1-

    new tools for precision medicine

    2021  Volume 15

    Abstract: Abstract The discovery of the Cystic fibrosis (CF) gene in 1989 has paved the way for incredible progress in treating the disease such that the mean survival age of individuals living with CF is now ~58 years in Canada. Recent developments in gene ... ...

    Abstract Abstract The discovery of the Cystic fibrosis (CF) gene in 1989 has paved the way for incredible progress in treating the disease such that the mean survival age of individuals living with CF is now ~58 years in Canada. Recent developments in gene targeting tools and new cell and animal models have re-ignited the search for a permanent genetic cure for all CF. In this review, we highlight some of the more recent gene therapy approaches as well as new models that will provide insight into personalized therapies for CF.
    Keywords Cystic fibrosis ; Stem cells ; Lung ; Organoids ; CFTR ; Alternative chloride channels ; Medicine ; R
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2

    Huibi Cao / Juntao Mai / Zhichang Zhou / Zhijie Li / Rongqi Duan / Jacqueline Watt / Ziyan Chen / Ranmal Avinash Bandara / Ming Li / Sang Kyun Ahn / Betty Poon / Natasha Christie-Holmes / Scott D. Gray-Owen / Arinjay Banerjee / Karen Mossman / Rob Kozak / Samira Mubareka / James M. Rini / Jim Hu /
    Jun Liu

    Cell & Bioscience, Vol 11, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Abstract Background The ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all ... ...

    Abstract Abstract Background The ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Results Here, we describe a novel, intranasally delivered COVID-19 vaccine based on a helper-dependent adenoviral (HD-Ad) vector. The vaccine (HD-Ad_RBD) produces a soluble secreted form of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and we show it induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. Conclusion Our approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.
    Keywords COVID-19 ; HD-Ad ; Nasal delivery ; SARS-CoV2 ; Vaccine ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Epithelium-Specific Ets-Like Transcription Factor 1, ESE-1, Regulates ICAM-1 Expression in Cultured Lung Epithelial Cell Lines

    Zhiqi Yu / Jun Xu / Jinbao Liu / Jing Wu / Chan Mi Lee / Li Yu / Jim Hu

    Mediators of Inflammation, Vol

    2015  Volume 2015

    Keywords Pathology ; RB1-214 ; Medicine ; R
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Activation of P2X(7) receptor by ATP plays an important role in regulating inflammatory responses during acute viral infection.

    Benjamin H Lee / David M Hwang / Nades Palaniyar / Sergio Grinstein / Dana J Philpott / Jim Hu

    PLoS ONE, Vol 7, Iss 4, p e

    2012  Volume 35812

    Abstract: Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to ... ...

    Abstract Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to devastating consequences. Macrophages are important innate immune cells that recognize viruses and induce inflammatory responses at the early stage of infection. However, tissue resident macrophages are not easily activated by the mere presence of virus suggesting that their activation requires additional signals from other cells in the tissue in order to trigger inflammatory responses. Previously, we have shown that the cross-talk between epithelial cells and macrophages generates synergistic inflammatory responses during adenoviral vector infection. Here, we investigated whether ATP is involved in the activation of macrophages to induce inflammatory responses during an acute adenoviral infection. Using a macrophage-epithelial cell co-culture system we demonstrated that ATP signaling through P2X(7) receptor (P2X(7)R) is required for induction of inflammatory mediators. We also showed that ATP-P2X(7)R signaling regulates inflammasome activation as inhibition or deficiency of P2X(7)R as well as caspase-1 significantly reduced IL-1β secretion. Furthermore, we found that intranasal administration of replication deficient adenoviral vectors in mice caused a high mortality in wild-type mice with symptoms of acute respiratory distress syndrome but the mice deficient in P2X(7)R or caspase-1 showed increased survival. In addition, wild-type mice treated with apyrase or inhibitors of P2X(7)R or caspase-1 showed higher rates of survival. The improved survival in the P2X(7)R deficient mice correlated with diminished levels of IL-1β and IL-6 and reduced neutrophil infiltration in the early phase of infection. These results indicate that ATP, released during viral infection, is an important inflammatory regulator that activates the inflammasome pathway and regulates ...
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Modulation of Alloimmune Responses by Interleukin-10 Prevents Rejection of Implanted Allogeneic Smooth Muscle Cells and Restores Postinfarction Ventricular Function

    Sanjiv Dhingra / Jun Wu / Shu-Hong Li / Jian Guo / Xi-Ping Huang / Anton Mihic / Jim Hu / Richard D. Weisel / Ren-Ke Li M.D., Ph.D.

    Cell Transplantation, Vol

    2015  Volume 24

    Abstract: Interleukin-10 (IL-10) gene transduction into allogeneic smooth muscle cells (SMCs) was evaluated to improve the long-term benefits of allogeneic cell transplantation into infarcted myocardium. Allogeneic cells, including SMCs, have been demonstrated to ... ...

    Abstract Interleukin-10 (IL-10) gene transduction into allogeneic smooth muscle cells (SMCs) was evaluated to improve the long-term benefits of allogeneic cell transplantation into infarcted myocardium. Allogeneic cells, including SMCs, have been demonstrated to restore cardiac function and repair the infarcted myocardium, but late rejection of the transplanted cells by the host immune system may reverse the benefits of cell therapy. In a rat myocardial infarction model, three groups of rats were injected with either unmodified autologous, unmodified allogeneic, or allogeneic + IL-10 SMCs into the infarct region. Three weeks later, most of the allogeneic cells were rejected, whereas autologous cells were engrafted in the myocardium. IL-10 gene transduction of the allogeneic SMCs significantly improved the cell survival. To understand the mechanism of this improved survival, we evaluated the host immune responses against the SMCs. Allogeneic SMCs expressing IL-10 decreased leukocyte-mediated cytotoxicity in coculture, decreased the number of cytotoxic CD8 + T-cells, and increased the number of CD4 + CD25 + regulatory T-cells in vitro and in vivo. Furthermore, IL-10 prevented the production of antidonor antibodies by the recipients against the allogeneic SMCs. Transplantation of unmodified autologous SMCs, but not unmodified allogeneic SMCs, significantly improved fractional shortening and left ventricular dimensions compared to the media-injected control group. However, IL-10 gene-enhanced allogeneic SMCs improved ventricular function, increased wall thickness, and decreased scar length in association with their enhanced survival. We conclude that IL-10 gene-enhanced cell therapy with allogeneic SMCs prevents detrimental alloimmune responses in the recipient, thereby increasing the survival of transplanted allogeneic SMCs and more effectively restoring cardiac function.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2015-06-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Improved β-Glucuronidase Reporter for Mammalian Gene Expression Analysis

    Soo Chan / Jonathan Plumb / Jim Hu

    BioTechniques, Vol 27, Iss 5, Pp 896-

    1999  Volume 900

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 1999-11-01T00:00:00Z
    Publisher Future Science Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: System for PCR Identification of cDNA Ends (SPICE)

    David R. Koehler / Raymond Tellier / Jim Hu / Martin Post

    BioTechniques, Vol 27, Iss 1, Pp 46-

    1999  Volume 48

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 1999-07-01T00:00:00Z
    Publisher Future Science Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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