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HIV/AIDS
Published in Patricia G. Melloy, Viruses and Society, 2023
Over time, some people have emerged, sometimes known as outliers, who did not acquire HIV despite engaging in high-risk behaviors for acquiring HIV (Lostroh 2019). One such person was Stephen Crohn, who did not acquire HIV even though he may have been exposed to it many times. Scientists studied Crohn and found he possessed the rare delta 32 mutation in the HIV co-receptor CCR5 (Walker 2008a; Ojikutu 2008a). Unfortunately, Crohn took his own life in 2013 (Schwartz 2013). This mutation is very rare, and a person needs to have two copies of the delta 32 mutation to see the effect. Although the mutation is thought to have come from the Vikings in northern Europe originally, the mutation has been found in people with geographic origins in other parts of Europe as well as western Asia (Novembre, Galvani, and Slatkin 2005; Huang et al. 1996; Martinson et al. 1997). These human outliers can be important for understanding HIV/AIDS infection and trying to find new ways to stop the virus.
Current Application of CRISPR/Cas9 Gene-Editing Technique to Eradication of HIV/AIDS
Published in Yashwant Pathak, Gene Delivery, 2022
Prachi Pandey, Jayvadan Patel, Samarth Kumar
Recently, the birth of gene-edited babies in 2018 has aroused widespread criticism around the scientific fields. This is the time that the CCR5 gene edited by CRISPR-Cas9 human embryos were implanted into women to have HIV-1 resistant babies. This work would make a permanent change to the germ line, which might be passed on to the longer term generations. Obviously, this experiment didn’t meet the moral guideline concerning germline and embryo editing. Additionally, it lacks the rationale to switch CCR5 in human embryos, since HAART can inhibit HIV-1 replication. Also, the experimental couple can have a healthy baby. For HIV-positive mothers, cesarean delivery can protect babies from HIV infection. Even an HIV-positive father would not have any risk to transmit to the babies. Moreover, a CCR5 edited baby cannot resist all HIV strains, since the virus can evolved to utilize CXCR4 as an alternative co-receptor. Finally, CRISPR/Cas9 technology has limitations in application, like off-target effects. The safety of heritable germline editing should be monitored and evaluated. The side effects of permanent editing of the CCR5 gene haven’t been reported, yet some researches have showed that CCR5 deficiency increases the chance of symptomatic West Nile viral infection.
Healthy People / Immuno-enhancement
Published in Jonathan Anomaly, Creating Future People, 2020
In 2018 Dr. He Jiankui claims to have used CRISPR to edit the CCR5 gene in the developing embryos of twin girls, whom he named Lulu and Nana. ‘Silencing’ this gene produces resistance to HIV, though the procedure was widely denounced because CRISPR often produces off-target mutations in other genes, and because the total effects of silencing CCR5 are still not known. In fact, just months after Dr. He’s announcement, scientific studies began reporting potential side effects of silencing CCR5. These include protection against cognitive decline with neurodegenerative diseases (Joy et al., 2019), but also a potential reduction in lifespan (Luban, 2019).
CCR5 is a potential therapeutic target for cancer
Published in Expert Opinion on Therapeutic Targets, 2021
Hossein Hemmatazad, Martin D. Berger
The C-C motif chemokine receptor 5 (CCR5) belongs to the beta chemokine receptor family and consists of 352 amino acids with a molecular mass of 40,524 kDa [19,20]. CCR5 is a transmembrane G-protein-coupled receptor, mainly expressed on activated T cells (Th1 and Th17), B cells, monocytes, macrophages, dendritic cells, myeloid-derived suppressor cells, regulatory T cells and natural killer cells. Furthermore, CCR5 expression is also observed in microglial cells, astrocytes, osteoclasts, hepatic stellate and endothelial cells, vascular smooth muscle cells, and fibroblasts but also in various tumor cells and cancer-associated fibroblasts (CAFs) [21–24]. The main physiological function of CCR5 is to recruit immune cells in order to orchestrate chemotaxis and to modulate immune responses upon inflammatory stimuli [16,25]. Additionally, CCR5 serves as a crucial co-receptor for HIV to enter host cells [26].
Revising, Correcting, and Transferring Genes
Published in The American Journal of Bioethics, 2020
Consider the differences between the recent horrendous experiment by the biophysicist He Jiankui, and other existing translational research on germline gene editing. He Jiankui used the CRISPR gene editing platform3 to induce a rare mutation of the gene CCR5 (CCR5-Δ32) in embryos that were then used to create a pregnancy (Regalado 2018). The intention was to render two twin girls homozygous for CCR5-Δ32, which appears to have failed (Regalado 2019b). The mutation is rare, and its effects on physiology and development are not completely known. It is believed, for instance, that CCR5-Δ32 is involved in neurological development and specifically in memory; individuals with the mutation appear to perform better on memory tests and recover more quickly from stroke (Joy et al. 2019). CCR5-Δ32 also confers immunity to HIV infection. The gametes that were used to create the zygotes in this experiment came from an HIV positive father and an HIV negative mother. He Jiankui’s stated aim was to prevent vertical HIV transmission during pregnancy, something for which there are already other good preventative options (Cyranoski and Ledford 2018).
Emerging therapeutics for the management of COVID 19
Published in Expert Opinion on Emerging Drugs, 2020
Sujit Kumar Debnath, Rohit Srivastava, Abdelwahab Omri
Leronlimab acts as a C-C chemokine receptor type-5 (CCR5) antagonist which works by blocking calcium channel signaling. CCR5 is an immunological receptor which is present on the surface of different cells [115]. Leronlimab is also used as adjuvant therapy in the treatment of metastatic triple-negative breast cancer [116]. CytoDyn, the inventor of leronlimab filed the Investigational New Drug (IND) application with the FDA in March 2020 and got approval to initiate a phase II trial to explore the use of it against coronavirus. The company noticed a gradual increase in CD8 T-lymphocyte percentage by day 3 of treatment and successfully reduce the production of IL-6 in infected patients [117]. Recently, 54 patients were recruited to the FDA-approved clinical trials of which 49 patients received leronlimab. This company has reported that the majority of treated patients have demonstrated remarkable recoveries from COVID-19 infection [118].