Morpholinos in pretargeting and crosslinking applications
"Pretargeting" is the use of a Morpholino conjugated to an antibody to bind a particular antigen (e.g. a tumor marker) followed later by a complementary Morpholino conjugated to a radioisotope or other effector molecule. The high molecular mass antibody conjugate clears the blood slowly, but does not damage the body during its residence in the blood. The low molecular mass Morpholino-cargo conjugate binds rapidly with good affinity to the complementary Morpholino on the antigen-bound antibody, but remaining free Morpholino-cargo conjugate clears the blood quickly. If a radio-labeled oligo is used this keeps the radiation dose well below what it would be if a slowly-clearing radio-labeled antibody were used, but provides the binding specificity of an antibody-based targeting method. Non-radioactive cargos can be delivered in enhanced quantity by attaching numerous Morpholino molecules to the pretargeting antibody Crosslinking involves treatment with Morpholino-linked antibodies that bind a surface marker of a cell, then following that with complementary Morpholinos linked to a polymer scaffold. This causes aggregation of the surface marker in small regions of the cell surface as the antibody-linked Morpholinos bind the scaffold-linked complementary Morpholinos, in some cases increasing apoptosis. References Gambles MT, Li S, Kendell I, Li J, Sborov D, Shami P, Yang J, Kopeček J. Multiantigen T-Cell Hybridizers: A Two-Component T-Cell-Activating Therapy. ACS Nano. 2024 Aug 16. doi: 10.1021/acsnano.4c06500. Online ahead of print. PMID: 39149859 Liu G, Dou S, Pretorius PH, Liu X, Chen L, Rusckowski M, Hnatowich DJ. Tumor pretargeting in mice using MORF conjugated CC49 antibody and radiolabeled complimentary cMORF effector. 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