# Aptamer-Based Delivery of Genes and Drugs Across the Blood–Brain Barrier

## TL;DR

Aptamers can help deliver drugs and genes across the blood-brain barrier, offering new hope for treating neurological diseases.

## Contribution

The paper reviews recent advances in aptamer design and delivery methods for central nervous system disorders.

## Key findings

- Aptamers can cross the blood-brain barrier via receptor-mediated transcytosis.
- Recent techniques like in vivo SELEX and nanoparticle–aptamer hybrids improve brain delivery efficiency.
- Aptamers show promise for treating Alzheimer’s, Parkinson’s, and brain cancers.

## Abstract

The blood–brain barrier (BBB) restricts therapeutic delivery to the central nervous system (CNS), hindering the treatment of neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, brain cancers, and stroke. Aptamers, short single-stranded DNA or RNA oligonucleotides that can fold into unique 3D shapes and bind to specific target molecules, offer high affinity and specificity, low immunogenicity, and promising BBB penetration via receptor-mediated transcytosis targeting receptors such as the transferrin receptor (TfR) and low-density lipoprotein receptor-related protein 1 (LRP1). This review examines aptamer design through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and its variants, mechanisms of BBB crossing, and applications in CNS disorders. Recent advances, including in silico optimization, in vivo SELEX, BBB chip-based MPS-SELEX, and nanoparticle–aptamer hybrids, have identified brain-penetrating aptamers and enhanced the brain delivery efficiency. This review highlights the potential of aptamers to transform CNS-targeted therapies.