Rosy prospects
Brain expression of Transferrin Receptor, a favorite nanotech target, targeted by Spike
Medical publications weighing in on greatest hits like ‘bat soup from the market’ and ‘stays in the arm’… connected with my other posts…
The most common target when designing brain delivery:
Targeting the transferrin receptor for brain drug delivery
Johnsen KB, Burkhart A, Thomsen LB, Andresen TL, Moos T. Prog Neurobiol. 2019 Oct;181:101665. doi: 10.1016/j.pneurobio.2019.101665.
“Obtaining efficient drug delivery to the brain remains the biggest challenge ... The main obstacle is the blood-brain barrier (BBB), which impedes the entrance of most molecules ... To overcome this obstacle, targeting strategies binding to nutrient receptors present at the luminal membrane of the BBB are frequently employed. Amongst the numerous potential targets at the BBB, the transferrin receptor (TfR) remains the most common target used to ensure sufficient drug delivery to the brain. In this review, we provide a full account on the use of the TfR as a target for brain drug delivery by describing the function of the TfR in the BBB, the historical background of its use…”
‘Targeted’ = ‘across’
Transferrin-conjugated nanoparticles of poly(lactide)-D-alpha-tocopheryl polyethylene glycol succinate diblock copolymer for targeted drug delivery across the blood-brain barrier
Gan CW, Feng SS.Biomaterials. 2010 Oct;31(30):7748-57. doi:10.1016/j.biomaterials.2010.06.053.
What waits for us ‘across’ the blood-brain barrier?
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Human Protein Atlas: Expression of Transferrin Receptor 1 in brain
White = not expressed, Light Rose = slightly expressed, Dark Rose = highly expressed
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‘Any cell’ (e.g., the rosy pink ones):
The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory.
Ndeupen S, Qin Z, Jacobsen S, Bouteau A, Estanbouli H, Igyártó BZ. iScience. 2021 Dec 17;24(12):103479. doi: 10.1016/j.isci.2021.103479
Image: “Any cell expressing and presenting vaccine peptides / proteins can become target of T cell and NK cell-mediated killing.”
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Spike uses the Transferrin Receptor, as do HIV and Adenovirus:
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The most common target when designing brain delivery is targeted by Spike:
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Ferristatin II Efficiently Inhibits SARS-CoV-2 Replication in Vero Cells
Alexey Sokolov, Irina Isakova-Sivak, Natalia Grudinina, Daria Mezhenskaya, Elena Litasova, Valeria Kostevich, Ekaterina Stepanova, Alexandra Rak, Ivan Sychev, Olga Kirik, Larisa Rudenko. Viruses. 2022 Feb 3;14(2):317. DOI: 10.3390/v14020317
“…Multiple mechanisms for SARS-CoV-2 cell entry have been described; however, the role of transferrin receptor 1 (TfR1) in SARS-CoV-2 infection has received little attention. We used ferristatin II to induce the degradation of TfR1 on the surface of Vero cells and to study the consequences of such treatment on the viability of the cells and the replication of SARS-CoV-2. … The uptake of RBD protein is nearly fully inhibited by ferristatin II treatment, although this protein remains bound on the cell surface. The findings were well confirmed by the significant inhibition of the SARS-CoV-2 infection of Vero cells by ferristatin II …. We hypothesize that ferristatin II blocks the TfR1-mediated SARS-CoV-2 host cell entry … The inhibition of viral entry by targeting the receptor on the host cells, rather than the viral mutation-prone protein, is a promising COVID-19 therapeutic strategy.”
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