TfR is expressed ubiquitously in many organs
- TfR (CD71) is ubiquitously expressed in normal cells, including the endothelium of brain capillaries, hepatocytes, and kidney and particularly abundant in maturing erythroid cells. TfR (CD71) expression in skeletal and cardiac muscle is exceptionally high, and silencing is observed at the organ.
- Considering that cell populations with high TfR(CD71) expression can be target cells in other organs as well, many tissues can be considered for our antibody/nucleic acid conjugates.
- We were the first to report that anti-TfR antibody-nucleic acid conjugates can deliver nucleic acids to muscle tissue.
Development of Antibody-siRNA Conjugate Targeted to Cardiac and Skeletal Muscles
Journal of Controlled Release 237, p1-13, 2016.
Cellular Uptake and Intracellular Trafficking of our Conjugates
- Our anti-TfR (CD71) antibody (fragment) nucleic acid conjugates can escape from endosomes after being taken up into the cell by endocytosis.
Size
- Our anti-TfR antibody (fragment) nucleic acid conjugates are small enough (diameter: 3.5-15 nm) to pass through capillary walls and reach and penetrate target tissues.
- Compared to Lipid Nanoparticles (LNPs ~100 nm), which are large enough to leak only through the sinusoidal endothelial cell pores common in the liver, our anti-TfR antibody (fragment) nucleic acid conjugates can target a variety of organs.
- However, its size is such that it can escape kidney elimination.
Permeability
- The size of the antibody fragment (Fab’) is about 7 nm, larger than the peptide (2-4 nm) and smaller than the whole antibody (15 nm). The particle size of the antibody fragments is larger than the filtration limit of the kidney (3-5 nm).
- Antibody fragments (Fab’) are smaller than whole antibodies and have higher tissue permeability.
- From the data below, we understand that our Fab’-siHPRT penetrates the left ventricle, a thick tissue, and uniformly suppresses gene expression.
