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Antisense oligonucleotides (ASOs) have emerged as promising therapeutic candidates, and numbers of preclinical studies with PD models have demonstrated their potential to inhibit \u03b1\u2010synuclein aggregation. However, a major obstacle to clinical application of ASOs in neurodegenerative diseases is their limited permeability across the blood\u2013brain barrier. Consequently, currently approved ASOs for neurological disorders are administered intrathecally, which makes it difficult to achieve efficient drug delivery to deep brain structures such as the basal ganglia. Focused ultrasound (FUS)\u2010induced blood\u2013brain barrier opening has attracted interest as a noninvasive strategy to enhance central nervous system drug delivery. Clinical studies have demonstrated that FUS\u2010mediated blood\u2013brain barrier opening can be performed safely in patients with PD and effective delivery of therapeutic agents, such as glucocerebrosidase. Yet, evidence for effective delivery of ASOs to the brain via FUS\u2010induced blood\u2013brain barrier opening is still lacking. This review summarizes current studies of ASOs in PD, together with recent advances in FUS\u2010mediated blood\u2013brain barrier opening. We highlight remaining biological and translational limitations and outline future perspectives for optimizing ASOs delivery with FUS\u2010mediated blood\u2013brain barrier opening to accelerate disease\u2010modifying therapy for PD.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70445-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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