Duchenne muscular dystrophy (DMD) remains a major challenge for drug developers because many therapeutic approaches have struggled to deliver sufficient amounts of a treatment to skeletal and cardiac muscle while maintaining an acceptable safety profile. Against this backdrop, South Korean biotechnology company HLB Panagene is exploring a different strategy based on a peptide nucleic acid (PNA)-based antibody-oligonucleotide conjugate (AOC) platform.
AOC is an emerging therapeutic modality derived from the concept of antibody-drug conjugates (ADCs). Instead of carrying a conventional cytotoxic drug, an AOC uses an antibody to deliver a nucleic-acid-based therapeutic payload to specific cells. The goal is to combine the targeting capability of antibodies with the ability of nucleic acids to regulate gene expression.
One of the major challenges with nucleic-acid therapeutics is delivery. These molecules generally have limited ability to cross cell membranes. Even when they enter cells through antibody-mediated delivery, they can become trapped inside endosomes or be degraded before reaching their intended intracellular target. HLB Panagene believes that PNA could help address some of these limitations because of its structural stability and strong target-binding characteristics.
The company has selected DMD as the first disease indication for validating its PNA-AOC platform. Its approach is particularly relevant to exon-skipping therapy, where an oligonucleotide is designed to modify dystrophin pre-mRNA processing and allow cells to produce a shorter but potentially functional dystrophin protein. HLB Panagene is pursuing an AOC architecture intended to improve delivery of an exon-skipping PNA to muscle tissue. Industry reports indicate that a transferrin receptor 1 (TfR1) antibody is being explored as part of the delivery strategy, with a preclinical proof-of-concept targeted for 2026.
The strategy comes as several existing DMD therapeutic approaches have encountered limitations involving efficacy, delivery or safety. Other companies are also developing targeted oligonucleotide delivery technologies, including AOC-based programs, suggesting that delivery efficiency has become one of the central battlegrounds in next-generation DMD drug development.
| Подход | Payload | Delivery strategy | DMD target | Development stage |
|---|---|---|---|---|
| Traditional exon skipping | ОУП | Systemic | Specific exons | Одобренный |
| AOC approach | Oligonucleotide | Antibody-mediated | Muscle | Clinical development |
| ПНА-АОК | PNA | Antibody-mediated | Muscle | Early/preclinical |
| Генная терапия | Микродистрофин | ААВ | Broad muscle | Clinical/approved depending on product |
However, HLB Panagene’s PNA-AOC program remains early-stage. There is currently no approved PNA-AOC therapy for DMD, and the company’s approach still needs to demonstrate effective muscle delivery, exon-skipping activity, dystrophin restoration, safety and ultimately clinical benefit in human studies.
For DMD families, therefore, PNA-AOC should be viewed not as an available treatment, but as an experimental therapeutic platform worth monitoring. Its potential significance lies in attempting to solve one of the fundamental problems facing nucleic-acid therapies: getting the right therapeutic molecule to the right muscle cells at an effective and sustainable level.
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