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Genome Editing and Gene Therapies: Complex and Expensive Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Deng et al. (1996) described CCR5, a seven-transmembrane chemokine receptor, as the major co-receptor for HIV-1 entry used by most of the HIV in vivo strains, and since then CCR5 has been investigated as a target for HIV therapy. Twelve years later, Perez et al. (2008) reported that they succeeded in ZFNs-mediated permanent disruption of the CCR5 gene in primary human CD4+ T lymphocytes. In a mouse model (see Watanabe et al., 2007) primary CD4+ T cells were transduced using Ad5/35 vectors expressing the CCR5 ZFNs which conferred protection against HIV infection in vivo and in vitro as proven by CCR5 reconstitution experiments. Finally, in 2014, Tebas and colleagues reported about a successful clinical trial with 12 HIV patients treated with infusion of autologous CD4 T cells modified at CCR5 by a ZFN; the nonhomologous end joining repair of the induced DSBs rendered the CCR5 gene permanently dysfunctional. As a consequence of the partial induced genetic HIV resistance the CD4 T-cell counts increased significantly in these patients that in addition showed decreased levels of HIV DNA. One important conclusion drawn from this study was that CCR5-modified autologous CD4 T-cell infusions are safe.
A History of Flow Cytometry and Sorting
Published in Frances S. Ligler, Jason S. Kim, The Microflow Cytometer, 2019
One of the simplest flow cytometers now in widespread use, the BD FACSCount,50 is a relatively small instrument designed solely for the purpose of counting CD4-positive T cells and a few other relevant cell types in the peripheral blood of HIV/AIDS patients in resource-poor areas. The light source in the FACSCount is a 543 nm He-Ne laser emitting less than 1 mW, and the apparatus measures only two parameters, yellow-orange (PE) fluorescence and red (PE-Cy5) fluorescence, using relatively inexpensive photomultiplier detectors. For CD4 counting, the criterion used is the presence of both PE-Cy5-labeled antiCD3 and PE-labeled anti-CD4 on a cell; fluorescent beads added to the sample at known concentrations are used to derive the cell count per unit volume. The FACSCount has several competitors; among them are flow cytometers from Guava (Hayward, CA), Partee, and Pointcare Technologies (Marlborough, MA). All of these instruments cost at least a few tens of thousands of dollars, and a reasonably steady flow of manuscripts, grant applications, etc. across my desk suggests that there are a lot of other people trying to get into the CD4 counter business, many of them proposing to do so with microflow systems.
Osteoimmunomodulation with Biomaterials
Published in Nihal Engin Vrana, Biomaterials and Immune Response, 2018
Bengü Aktaş, Bora Garipcan, Zehra Betül Ahi, Kadriye Tuzlakoğlu, Emre Ergene, Pınar Yılgör Huri
B-cells are formed by HSCs in the bone marrow. They are responsible for producing antibodies. Firstly, BCRs bind the antigens, and antigens are engulfed into the B-cell and digested. Then cognate helper T-cells bind to B-cells and secrete lymphokines for mitosis and differentiation. Finally, B-cells differentiate into the plasma cell. Plasma cells are able to secrete large amounts of antibodies [22]. There are several kinds of T-cells. For example, T-helper cells (CD4+), the largest group of T-cells, stimulate the growth and proliferation of cytotoxic T-cells (CD8+). They also stimulate the growth and differentiation of B-cells and are responsible for activation of the macrophage system [23]. CD4+ T-cells might be infected by the human immunodeficiency virus (HIV). For this reason, the number of CD4+ T-cells decreases drastically and the ability of the immune response fails. Cytotoxic T-cells (CD8+), on the other hand, destroy virus-infected cells, tumour cells and cells that are transferred along with organ transplants.
Optimization of formulation and process variables using central composite design for the production of nevirapine spray dried solid dispersion
Published in Drying Technology, 2022
Ashok Mahajan, Naazneen Surti, Priyal Patel, Naziya Gheewala, Ashwini Patel, Dimal Shah
Acquired immunodeficiency syndrome (AIDS) is an advanced stage of human immunodeficiency virus (HIV) infection. HIV is a lentivirus which attacks human immune system by reducing CD4 cells, a type of T cells. This leads to progressive failure of the immune system that allows life-threatening infections and cancers to thrive.[1,2] According to UNAIDS, the number of cases of HIV/AIDS infection, across the globe, were found to be approximately 37.9 million. Out of these, 36.2 million were adults and 1.7 million were children (<15 years old).[3]