Regulatory autoantibodies binding to G protein-coupled receptors (RAb-GPCRs) are increasingly recognized as physiological players in the regulation of GPCR functions. By specifically binding to GPCRs, they are able to activate or inhibit their signaling. However, under certain conditions they may become dysregulated or upregulated which can lead to persistent and uncontrolled activation of GPCRs.
Research has linked RAbs to a wide range of diseases, including autoimmune diseases (like systemic sclerosis and lupus), cardiovascular and cerebrovascular diseases, and neuroimmunologic disorders (like myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID syndrome).
G protein-coupled receptors are involved in many physiological processes within the human body. Their extensive physiological relevance and druggability has made GPCRs a major target for drug innovation and more than 30% of all FDA-approved drugs act through GPCRs, underlining their significance in disease management and drug development.
The complexity of GPCR signaling, coupled with the wide cellular distribution of these receptors, makes dysregulated RAb-mediated interference particularly harmful, underscoring the opportunity of new therapies targeting these regulatory autoantibodies.
Rovunaptabin is a single-stranded DNA aptamer consisting of 15 deoxynucleotides that forms well-defined three-dimensional configuration, binding with high affinity and specificity to regulatory autoantibodies (RAbs) preventing them from activating GPCRs. This mechanism may also lead to a reduction in further production of RAbs.
Rovunaptabin is a single-stranded DNA aptamer consisting of 15 deoxynucleotides that forms well-defined three-dimensional configuration, binding with high affinity and specificity to regulatory autoantibodies (RAbs) preventing them from activating GPCRs. This mechanism may also lead to a reduction in further production of RAbs.
Aptamers are short, single-stranded oligonucleotides (either DNA or RNA) that fold into defined architectures and bind specifically to target molecules such as antibodies and other proteins. They are synthetically made, allowing precise control over their composition in a readily scalable process and have a high degree of stability.
Aptamers are generally less immunogenic than protein-based therapeutics. Aptamers can also be easily modified with various chemical groups to improve their properties and functionality and due to their small size, aptamers can penetrate tissues more efficiently than larger molecules like antibodies. Given these advantages, aptamers offer a promising new approach to targeted therapies with potential advantages over drug modalities.
Rovunaptabin (formerly BC 007) is our lead candidate aptamer drug targeting regulatory autoantibodies and is currently in clinical development for heart failure and post viral infectious diseases.