Human Pituitary Tumour Transforming Gene 1 (PTTG1) is a 23 kDa protein that functions as a global transcription factor and is known to be overexpressed in various cancers, including breast and colorectal cancer, making it a promising diagnostic marker. Importantly, PTTG1 also plays a therapeutic role, as it has been shown to promote metastasis in breast cancer through the transactivation of CXCR2, a key molecule involved in tumour progression. Despite its critical role in cancer development, there is currently no effective molecular tool available to specifically recognise or inhibit PTTG1. This highlights the urgent need to develop a targeted molecular recognition element that can bind to and potentially block PTTG1, for both diagnostic and therapeutic applications in cancer management.

The solution is to use aptamers, which are single-stranded nucleic acids that can bind specifically to target proteins like PTTG1, a marker linked to cancer. Aptamers have many advantages over antibodies, they are cheaper to make, more consistent, and can be easily modified for different uses. They have already been used in diagnostic tools like OTA-sense (for detecting toxins) and CibusDx (for food pathogens), and in therapies, with several aptamers in clinical trials and one (Macugen) already approved. By creating an aptamer that targets PTTG1, this project aims to provide a new tool for cancer diagnosis and treatment, especially for cancers like breast and colorectal cancer, where PTTG1 is overexpressed.

The innovation in this project is the development of a novel aptamer called SECURA-3, specifically designed to target PTTG1, a cancer-related protein. Unlike traditional antibodies, SECURA-3 is a synthetic nucleic acid molecule with a unique secondary structure that includes a hairpin loop, bulge loop, internal loop, and external loop, allowing for strong and specific binding. SECURA-3 shows high affinity to PTTG1, with a dissociation constant of 16.41 ± 6.4 nM, and has been functionalised with a poly A-tail and a biotinylated oligo dT to support various downstream applications. Importantly, it demonstrates better tissue penetration in PTTG1-based histostaining than antibodies and also shows antagonistic activity, disrupting the interaction between PTTG1 and the CXCR2 enhancer sequence. This makes SECURA-3 a highly promising tool for both cancer diagnostics and targeted therapy.