Work

Novel aptamers targeting heparan sulfate for delivery of RNA therapeutics in Alzheimer’s disease

Year: 2026

Type: article

Abstract: Heparan sulfate (HS) proteoglycans are abundant, sulfation-patterned glycosaminoglycans on brain cells and the neurovascular unit that interact with amyloid- β (A β ) 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’s 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— in silico HS motif mapping and machine learning-guided sequence design through microfluidic/ in-vivo SELEX, site-specific chemical modification for nuclease resistance and blood–brain barrier transcytosis, to scalable GMP manufacture. Aptamer-HS technology could enable the precision delivery of RNA therapeutics in AD.

Source: Progress in Biomedical Engineering

DOI: 10.1088/2516-1091/ae7eb9

Authors: Arshad Mehmood, Amir Zaman Shah, Jesus Alejandro Martinez Juarez, Xiaohui Liu, Hui Jiang, Xuemei Wang

Institutions: State Key Laboratory of Digital Medical Engineering, Southeast University, Yangzhou University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,680