{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Amero P"],"funding":["Division of Chemistry","American Cancer Society","National Cancer Institute","NCI NIH HHS","University of Texas MD Anderson Cancer Center","John P. Gaines Foundation"],"pagination":["7655-7670"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12486140"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["143(20)"],"pubmed_abstract":["Aptamers, synthetic single-strand oligonucleotides that are similar in function to antibodies, are promising as therapeutics because of their minimal side effects. However, the stability and bioavailability of the aptamers pose a challenge. We developed aptamers converted from RNA aptamer to modified DNA aptamers that target phospho-AXL with improved stability and bioavailability. On the basis of the comparative analysis of a library of 17 converted modified DNA aptamers, we selected aptamer candidates, GLB-G25 and GLB-A04, that exhibited the highest bioavailability, stability, and robust antitumor effect in <i>in vitro</i> experiments. Backbone modifications such as thiophosphate or dithiophosphate and a covalent modification of the 5'-end of the aptamer with polyethylene glycol optimized the pharmacokinetic properties, improved the stability of the aptamers <i>in vivo</i> by reducing nuclease hydrolysis and renal clearance, and achieved high and sustained inhibition of AXL at a very low dose. Treatment with these modified aptamers in ovarian cancer orthotopic mouse models significantly reduced tumor growth and the number of metastases. This effective silencing of the phospho-AXL target thus demonstrated that aptamer specificity and bioavailability can be improved by the chemical modification of existing aptamers for phospho-AXL. These results lay the foundation for the translation of these aptamer candidates and companion biomarkers to the clinic."],"journal":["Journal of the American Chemical Society"],"pubmed_title":["Conversion of RNA Aptamer into Modified DNA Aptamers Provides for Prolonged Stability and Enhanced Antitumor Activity."],"pmcid":["PMC12486140"],"funding_grant_id":["5U01CA213759-02","P30CA016672","P30 CA016672","U01 CA213759","P50 CA127001","P50CA217685","P50CA127001","P50 CA217685","CHE-1411859"],"pubmed_authors":["Sood AK","Ivan C","Franciscis V","Lokesh GLR","Elsayed AM","Zhang S","Volk DE","Schubert T","Montalvo-Gonzalez E","Rodriguez-Aguayo C","Cardenas-Zuniga R","Cristini V","Lopez-Berestein G","Amero P","Wang Z","Mitra R","Chaudhari RR","Attia YM"],"additional_accession":[]},"is_claimable":false,"name":"Conversion of RNA Aptamer into Modified DNA Aptamers Provides for Prolonged Stability and Enhanced Antitumor Activity.","description":"Aptamers, synthetic single-strand oligonucleotides that are similar in function to antibodies, are promising as therapeutics because of their minimal side effects. However, the stability and bioavailability of the aptamers pose a challenge. We developed aptamers converted from RNA aptamer to modified DNA aptamers that target phospho-AXL with improved stability and bioavailability. On the basis of the comparative analysis of a library of 17 converted modified DNA aptamers, we selected aptamer candidates, GLB-G25 and GLB-A04, that exhibited the highest bioavailability, stability, and robust antitumor effect in <i>in vitro</i> experiments. Backbone modifications such as thiophosphate or dithiophosphate and a covalent modification of the 5'-end of the aptamer with polyethylene glycol optimized the pharmacokinetic properties, improved the stability of the aptamers <i>in vivo</i> by reducing nuclease hydrolysis and renal clearance, and achieved high and sustained inhibition of AXL at a very low dose. Treatment with these modified aptamers in ovarian cancer orthotopic mouse models significantly reduced tumor growth and the number of metastases. This effective silencing of the phospho-AXL target thus demonstrated that aptamer specificity and bioavailability can be improved by the chemical modification of existing aptamers for phospho-AXL. These results lay the foundation for the translation of these aptamer candidates and companion biomarkers to the clinic.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2026-06-04T01:49:44.477Z","creation":"2026-05-04T03:14:05.154Z"},"accession":"S-EPMC12486140","cross_references":{"pubmed":["33988982"],"doi":["10.1021/jacs.9b10460"]}}