AM Biotechnologies (AM) is developing an easy-to-use kit that enables a technician in a life science laboratory to rapidly develop renewable X-Aptamer (XA) affinity reagents at a reasonable price. Affinity reagents are widely used in research, diagnostic, and clinical applications. Antibodies are currently the most common affinity reagents; however, every aspect of the life science market has experienced problems with them including aggregation, precipitation, difficult quality control, batch-to-batch reproducibility issues, short shelf life, eed for cold storage, costly production, and permanent denaturation. X-Aptamers address every antibody limitation. The X-Aptamer Selection Kit has three basic components: 1) a microbead-based oligonucleotide library; 2) a set of reagents for selecting XAs to a target of interest; and ) a few simple hardware items used for XA selection. X-Aptamers are comprised of a DNA scaffold that incorporates non-DNA functional groups such as amino acid side chains and small molecules that interact with a target more robustly than standard DNA. XAs are developed in a proprietary, single-round, bead-based selection process using equipment found in virtually any life science laboratory. The process enables the selection of chemically-modified affinity reagents that cannot be enzymatically generated, which clears the way for a wide array of chemical functional groups that have never before been used in aptamer-based affinity agent selections. Several chemical functional groups have been tested to date and have resulted in X-Aptamers with low picomolar binding affinity. In addition, using XA processes, the binding affinity of a small molecule was improved by a million-fold. While extraordinary results have been obtain to date, there is a strong need to evaluate and optimize combinations of functional groups that hold the potential for creating protein affinity reagents with unmatched affinity, specificity, physical stability, and robust manufacturability. In this project, AM will develop and evaluate multiple chemically-modified library designs for selecting XAs to diverse protein targets and will develop robust methods for selecting ligand-modified XAs to ligand-binding protein targets. Successful completion of this Phase I project will set the stage for a Phase II project to optimize the X-Aptamer Selection Kit processes for commercialization in Phase III.
Public Health Relevance Statement: Public Health Relevance: The X-Aptamer Selection Kit will enable the life science market to quickly and easily develop chemically-synthesized, renewable affinity reagents that rival the performance of the best biologically-produced antibodies. X-Aptamers will address almost all limitations associated with widely-used antibodies and have the potential to lead to more effective diagnostics as well as new classes of therapeutic drugs.
NIH Spending Category: Biotechnology
Project Terms: Address; Affinity; Amino Acids; Antibodies; aptamer; arginyllysine; Aromatic Amino Acids; Aspartate; base; Binding (Molecular Function); Binding Proteins; Biological Sciences; Biotechnology; Cell Nucleus; Characteristics; Charge; chemical group; Chemicals; Chemistry; clinical application; commercialization; Communities; Cryopreservation; design; Diagnostic; Diagnostics Research; DNA; Ensure; Equipment; Exercise; experience; folate-binding protein; Frequencies (time pattern); functional group; Generic Drugs; Glutamates; Guanidines; improved; Indoles; inter-alpha-inhibitor; interest; Investigation; Isoelectric Point; Laboratories; Lead; Libraries; Life; Ligand Binding; Ligands; Marketing; Medical; Methods; Microspheres; Modification; Nucleic Acids; Nucleotides; Oligonucleotides; Performance; Pharmaceutical Preparations; Phase; phase 2 study; Phenols; phosphorodithioic acid; Post-Translational Protein Processing; Precipitation; Price; Process; Production; Protein Binding; Proteins; Protocols documentation; public health relevance; Quality Control; Reagent; Reproducibility; research and development; Retinol Binding Proteins; Route; scaffold; Side; small molecule; Specificity; Staging; System; Testing; Texas; Therapeutic; time use; Tryptophan; Tyrosine; Universities; Vertebral column
