Targeting ocular tissues with intravenously administered aptamers selected by in vivo SELEX

• Main Authors: Sonja Korhonen (Author), Katja Stenberg (Author), Umair Seemab (Author), Piia Bartos (Author), Katariina Mäkiniemi (Author), Jørgen Kjems (Author), Daniel Miotto Dupont (Author), Astrid Subrizi (Author)
• Format: Book
• Published: Elsevier, 2024-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2162-2531; 10.1016/j.omtn.2024.102352
• Keywords: MT: Delivery Strategies; SELEX; aptamers; eye; ocular targeting; intravenous administration; Therapeutics. Pharmacology; RM1-950
• Source: Molecular Therapy: Nucleic Acids, Vol 35, Iss 4, Pp 102352- (2024)

Ocular diseases create a significant economic burden and decrease in quality of life worldwide. Drugs and carrier molecules that penetrate ocular tissues after intravenous administration are needed for more efficient and patient-friendly treatment of ocular diseases. Here, ocular barrier-penetrating aptamers were selected through the utilization of in vivo SELEX and intravenous injection in rats. Three aptamers-Apt1, Apt2, and Apt5-were chosen based on their specific accumulation in vascularized ocular tissues and further characterized for their in vivo biodistribution using quantitative reverse-transcription PCR (RT-qPCR). A statistically significant difference between ΔCt values of ocular and control tissues with Apt2 (p < 0.0001) and Apt5 (p < 0.0001) was observed. Interestingly, Apt1 was the most abundant aptamer in the sequencing pool, but it did not show a statistically significant difference in in vivo biodistribution between ocular and control tissues. Overall, this study established a functional in vivo SELEX method for discovering ocular tissue targeting aptamers.