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Biomed. Eng."],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Heparan sulfate (HS) proteoglycans are abundant, sulfation-patterned glycosaminoglycans on brain cells and the neurovascular unit that interact with amyloid-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) and tau, aggregate and propagate proteopathic species, and modulate cellular uptake pathways. Aptamers are short, chemically synthesized single-stranded nucleic acids that fold to form high-affinity ligands. Novel aptamers bind specific HS motifs for targeting ligands to deliver RNA therapeutics (siRNA, antisense oligonucleotides, mRNA, RNA aptamer-cargo hybrids) into the brain and diseased cells in Alzheimer\u2019s disease (AD). We cover diagnostic aptamers, systematic evolution of ligands by exponential enrichment (SELEX) approaches adapted for glycans and HS, chemistry, optimization (AI\/machine-learning-enabled design), novel therapeutic applications, delivery vehicles and conjugation strategies, catalytic aptamers\/ribozymes, and challenges for clinical translation. We propose a workflow\u2014\n                    <jats:italic>in silico<\/jats:italic>\n                    HS motif mapping and machine learning-guided sequence design through microfluidic\/\n                    <jats:italic>in-vivo<\/jats:italic>\n                    SELEX, site-specific chemical modification for nuclease resistance and blood\u2013brain barrier transcytosis, to scalable GMP manufacture. Aptamer-HS technology could enable the precision delivery of RNA therapeutics in AD.\n                  <\/jats:p>","DOI":"10.1088\/2516-1091\/ae7eb9","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:51:51Z","timestamp":1781736711000},"page":"032008","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel aptamers targeting heparan sulfate for delivery of RNA therapeutics in Alzheimer\u2019s disease"],"prefix":"10.1088","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7547-4767","authenticated-orcid":true,"given":"Arshad","family":"Mehmood","sequence":"first","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Zaman","family":"Shah","sequence":"additional","affiliation":[{"name":"College of Plant Protection, Yangzhou University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5971-1316","authenticated-orcid":true,"given":"Jesus Alejandro","family":"Martinez Juarez","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-758X","authenticated-orcid":false,"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6882-7774","authenticated-orcid":true,"given":"Xuemei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"prgbae7eb9bib1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115522","type":"journal-article","article-title":"Alzheimer\u2019s disease: insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs","volume":"211","author":"Monteiro","year":"2023","journal-title":"Biochem. 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