OhioMod2013:Design

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Design

Cell specificity

Anti-CD71 targets the transferrin receptors of common breast cancer.

For anti-cancer

• Antibodies targeting EGFRVIII, VEGFR,
• Folate

PEG-bis amine can react with NHS-activated folate to create folate-PEG amine

• RGD peptides - target alphaV integrins of the tumour vasculature.

For tissue specificity

• Use G-protein coupled receptor peptide ligand agonists.

In general, uptake into the cell can be improved by taking advantage of the cellular need to uptake iron (transferrin), folate, EGF, and other factors.

Nuclear pore entry

The origami may be tagged with various sequences or peptides in order to encourage nuclear envelope entry.

• SV40 72 bp sequence
• Use cationic NLS peptide sequences to bind to origami structure. However, they still need to be free enough to interact with importin.
• NF-kappaB binding sites demonstrate increased expression in calcium phosphate transfected cells[1]. Zeich's lab also showed that a hydrophobic coat alteration to a protein resulted in its ability to cross the NPC [2].
• If we use peptides, must be careful that there isn't an immune response against them.

OhioMod2013:Design/NuclearPore

References

1. Mesika A, Kiss V, Brumfeld V, Ghosh G, and Reich Z. Enhanced intracellular mobility and nuclear accumulation of DNA plasmids associated with a karyophilic protein. Hum Gene Ther. 2005 Feb;16(2):200-8. DOI:10.1089/hum.2005.16.200 |
2. Naim B, Zbaida D, Dagan S, Kapon R, and Reich Z. Cargo surface hydrophobicity is sufficient to overcome the nuclear pore complex selectivity barrier. EMBO J. 2009 Sep 16;28(18):2697-705. DOI:10.1038/emboj.2009.225 |