Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | DNA Aptamer-Polymer Conjugates for Selective Targeting of Integrin α4β1 T-Lineage Cancers. |
|---|---|
| Journal, issue, pages | ACS Appl Mater Interfaces, Vol. 17, Issue 3, Page 4543-4561, Year 2025 |
| Publish date | Jan 22, 2025 |
 Authors | Ian I Cardle / Jai Raman / Dinh Chuong Nguyen / Tong Wang / Abe Y Wu / Drew L Sellers / Trey J Pichon / Emmeline L Cheng / Nataly Kacherovsky / Stephen J Salipante / Michael C Jensen / Suzie H Pun /  |
| PubMed Abstract | Selective therapeutic targeting of T-cell malignancies is difficult due to the shared lineage between healthy and malignant T cells. Current front-line chemotherapy for these cancers is largely ...Selective therapeutic targeting of T-cell malignancies is difficult due to the shared lineage between healthy and malignant T cells. Current front-line chemotherapy for these cancers is largely nonspecific, resulting in frequent cases of relapsed/refractory disease. The development of targeting approaches for effectively treating T-cell leukemia and lymphoma thus remains a critical goal for the oncology field. Here, we report the discovery of a DNA aptamer, named HR7A1, that displays low nanomolar affinity for the integrin α4β1 (VLA-4), a marker associated with chemoresistance and relapse in leukemia patients. After truncation of HR7A1 to a minimal binding motif, we demonstrate elevated binding of the aptamer to T-lineage cancer cells over healthy immune cells. Using cryo-EM and competition studies, we find that HR7A1 shares an overlapping binding site on α4β1 with fibronectin and VCAM-1, which has implications for sensitizing blood cancers to chemotherapy. We last characterize barriers to aptamer translation, including serum stability, temperature-sensitive binding, and short circulation half-life, and synthesize an aptamer-polymer conjugate that addresses these challenges. Future work will seek to validate targeting of α4β1 tumors with the conjugate, establishing an aptamer-based biomaterial that can be readily adapted for targeted treatment of T-cell malignancies. |
 External links | ACS Appl Mater Interfaces / PubMed:39788927 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.5 Å |
| Structure data |  EMDB-45577: Cryo-EM Structural Analysis of Human Integrin Heterodimer bound to DNA Aptamer |
| Source |
|
Homo sapiens (human)