Approaches to optimize cell internalization and in vivo tumor homing by aptamer-drug conjugates using SELEX
Doherty, C. D.; Jain, S.; Bakken, K. K.; Wilbanks, B. A.; Ott, L. L.; Carlson, B. L.; Burgenske, D. M.; Sarkaria, J. N.; Maher, L. J.
Show abstract
Glioblastoma (GBM) is the most common primary malignant brain tumor and is typically fatal. GBM therapies are hindered by the impermeability of the blood brain barrier (BBB), the diffuse and infiltrative nature of the tumor, and the high heterogeneity of intratumoral GBM cells. Aptamers are short, synthetic, folded single strands of RNA or DNA or analogs that bind targets with high affinity and specificity. Aptamers are developed via the principles of natural selection, permitting an unbiased approach to therapeutic development. Thus, rather than using rational design to select a target and develop a targeting moiety, cycles of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) are employed in cell culture or in vivo to identify aptamers against unknown targets. Antibody drug conjugates (ADCs) have shown some efficacy for GBM but are limited by their large size and thus depend on leakiness of the BBB. We have recently applied in vivo SELEX to develop anti-GBM aptamers (six-fold smaller in mass than IgG antibodies) and to select aptamer-drug conjugates. Here we report attempts to focus aptamer selection toward internalizing drug-delivery targets and resulting challenges involving loss of tumor specificity in vivo.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Tandem-Cleavage Linkers Improve the In Vivo Stability and Tolerability of Antibody-Drug Conjugates 93%
- Welding PROxAb Shuttles: A modular approach for generating bispecific antibodies via site-specific protein-protein conjugation 92%
- Novel approaches to label the surface of S. aureus with DBCO for click chemistry-mediated deposition of sensitive cargo 91%
Similar papers in this journal
- Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance 93%
- Systemic Brain Tumor Delivery of Synthetic Protein Nanoparticles for Glioblastoma Therapy 91%
- Enhancing Intracellular Accumulation and Target Engagement of PROTACs with Reversible Covalent Chemistry 90%
Similar papers in this journal
- A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor specificity 92%
- Development of potent humanized TNFα inhibitory nanobodies for therapeutic applications in TNFα-mediated diseases 90%
- Tuning antibody stability and function by rational designs of framework mutations 90%
Similar papers in this journal
- Engineering affinity-matured variants of an anti-polysialic acid monoclonal antibody with superior cytotoxicity-mediating potency 91%
- Engineered protein-small molecule conjugates empower selective enzyme inhibition 91%
- Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.