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Aptamer-based Technology for Medical Diagnostic and Therapeutic Applications
The human body contains 206 bones and they make up the body's skeleton. Bones are living tissue where they are constantly going through cycles of renewal (i.e. bone remodeling cycle). The imbalance between bone formation and bone resorption will lead to different diseases, such as osteoporosis, osteogenesis imperfecta (OI, or otherwise known as “brittle bone disease”). Moreover, when there is an uncontrolled growth of cells inside the bone, bone tumors occur, which may eventually lead to bone cancer.
Aptamers are short RNA or single-stranded DNA molecules that can fold into unique three-dimensional conformations. Aptamers can bind specifically to their targets (e.g. specific type of cells or proteins) with high binding specificity and affinity. Therefore, they can be promising agents in both diagnostic and therapeutic applications.
The technology presents highly-specific aptamers as diagnostics and therapeutic agents for bone remodeling disorders and cancers including osteosarcoma and pancreatic cancer.
Technology Features, Specifications and Advantages
The technology provider has investigated the effect of the Sclerostin gene on bone formation under microgravity conditions in space. Sclerostin is a negative regulator of bone remodeling process, which inhibits bone formation.
A new class of molecule-nucleic acid aptamer against the Sclerostin protein has been identified and optimized. The selected aptamer can bind to Sclerostin and inhibit its activity. By inhibiting this negative regulator of bone remodeling, bone formation can be promoted.
Regarding the therapeutic applications, highly specific aptamers present a promising strategy for targeted delivery of cytotoxic natural products. Some of the current challenges are the low conjugation efficiency of aptamers to drugs and the chemical instability of conjugating linkers in liquid-phase reactions. These limitations have restrained the druggability of the aptamers.
In continuous efforts to address these challenges, the technology provider has developed novel aptamer-drug conjugates by combining aptamers with a conventional anti-cancer drug, Triptolide. This modification can improve Triptolide’s performance in targeting cancer cells with the aptamer’s specific affinity towards target cancer cells. This aptamer-conjugated format of the drug exhibits strong anti-cancer activity, low toxicity and side effects, good water solubility and bioavailability.
Aptamers are promising agents in both diagnostic and therapeutic applications. For example, they can be developed into potential drugs for preventing or treating bone loss.
One of the technology provider’s aptamer candidates for osteogenesis imperfecta therapy has been granted by the US-FDA for Orphan Drug Designation, which is a specific legislation designed to promote development of treatments for rare diseases.
Furthermore, specific aptamers have been identified and developed for targeting osteosarcoma (one of bone cancers) and pancreatic cancer cells. The technology provider will continue to develop highly specific aptamers for the diagnosis and treatment of cancers.
For patients with osteoporosis, brittle bone disease or other bone remodeling disorders, aptamer-based technology can be a potential treatment option.
For cancer patients, the highly specific aptamer-drug conjugates can achieve targeted delivery of drugs so as to achieve better anti-cancer effects with fewer side effects.