Aptamer & Aptazyme Services
Aptamer & Aptazyme Services
Admera Health provides services to develop aptamers and aptazymes using our proprietary technology platform AptaNxTM in support of a variety of applications including:
(e.g. imaging & tracking of biomolecules)
(e.g. companion diagnosis)
(e.g. a drug or a drug modulator)
Our next generation aptamer & aptazyme development technology, AptaNxTM, combines in vitro evolution with next generation sequencing (NGS), which can identify aptamers and aptazymes efficiently with high success rate.
In AptaNxTM, the ssDNA/RNA pool is incubated with the target molecule, which is then subjected to repetitive cycles (n=3-15) of “Bind, Partition, and Amplify”. The final enriched aptamer and aptazyme candidates are then identified by Next Generation sequencing (NGS).
A scheme of AptaNxTM technology platform is shown below:
The Advantages of Aptamer and Aptazyme
- An aptamer is a ssDNA or RNA, which binds its ligand with high affinity and specificity.
- An aptazyme consists of an aptamer module and a ribozyme module, in which ribozyme activity can be regulated by aptamer-ligand interaction. Thus an aptazyme can serve as a switch for controlling gene expressed when inserted into a gene cassette.
- The unique features of aptamers and aptazymes provide significant advantages and benefits for diagnostic and therapeutic development in comparison to antibodies.
- For diagnosis, aptamer-based assays have better sensitivity with broader dynamic range of detection for various biomarkers in comparison to immunoassays (e.g. ELISA).
- For therapeutics, aptamers and aptazymes may transform therapy (including immunotherapy) with optimal efficacy and minimal side effects by their unique feature of controllability.
The features of aptamers and antibodies are compared below:
|Composition||Four nucleotides (A,T/U, C, G with modifications)||22 amino acids|
|Size||5-30 KDa (15-100 nt)||150 KDa|
|Multivalency||Easily achievable||Difficult to achieve|
|Development||In vitro selection 4-12 weeks||In vivo immunization/hybridoma > 6 months|
|Production||Chemical synthesis, low cost||In vivo/hybridoma cell culture, high cost|
|Physical/thermal stability||Stable with long shelf-life||Unstable with limited shelf-life|
Admera Health has a team of wet-lab scientists and bioinformaticians specialized in aptazmer & aptazyme development. Our expertise is shown by selected case studies below:
Development of an aptasensor prototype for early detection of acute kidney injury using Lcn2 protein as a biomarker (PMID: 22946879).
Acute kidney Injury (AKI) is a global health burden affecting more than 13 million people worldwide. The lack of an early detection method prevents the patients from receiving prompt intervention. AKI has been shown to be detected by plasma/urine Lcn2 as early as 2 hours after the onset of AKI, allowing time for intervention. Using Lcn2 as a biomarker, Admera Health has developed an aptamer-based microcantilever biosensor prototype with potential for in-line monitoring of AKI.
Developed first aptamer-controllable chemistry (PMID: 19778045).
Aptamers can fold into coherent, yet malleable structures for ligand binding. Utilizing this unique feature of aptamer in a chemical reaction model of malachite green bleaching, Admera Health demonstrated that an aptamer can bind to a reactant and shield its reactive group from access by the other chemical in the reaction, thus controlling the chemical reaction in a dose and kinetics dependent manner. This discovery paves a novel way for controlling chemical reactivity by aptamers with potential implications in chemical synthesis and drug function control.
Admera Health has developed a technology platform RegCAR-TTM, in which aptazymes are developed as small molecule-dependent switches for controlling CAR expression in T-cells. The ability to control CAR expression has the potential to achieve maximal efficacy and minimal side-effects in CAR-T therapy. Utilizing Admera’s RegCAR-TTM technology platform, Admera Health has developed aptazymes responsive to FDA approved small chemical drugs for a top Biopharma, which enable our client to further developed controllable cell/gene therapy.
Development of a panel of aptamers for lung cancer diagnosis.
Low dose computed tomography (LDCT) is recommended for lung cancer screening for heavy smokers with ages of 55-88 years old. Although LDCT has been shown to save lives, it has high false positive rate (~30%), resulting in unnecessary biopsy and harms. Thus a method is in need to further diagnose the indeterminant nodules from LDCT. A panel of plasma protein markers has been shown with clinical utility for lung cancer diagnosis. For these biomarkers, Admera Health has developed a panel of aptamers with Kds in the range of nM. Further development of aptamer-based assay for this panel of protein markers may provide a noninvasive assay for lung cancer diagnosis and decrease the false positive rate in LDCT when combined to use. An aptamer-base assay for a panel of protein markers has potential advantages of multiplexing, high sensitivity, and broad dynamic range of detection.
Development of aptamers for inhibition of EBOV replication by breaking protein-protein interactions in its replication complex (PMID: 24067086)
Macromolecular interactions (e.g. protein/nucleic acid-protein interactions) provide ample opportunities for drug development, however, are often considered “undruggable” by small molecules. Unlikely small molecules, aptamers bind and interact extensively with their protein ligands, thus have potential to break protein/nucleic acid-protein interactions and inhibit their functions. Using VP35-NP interaction in the replication complex of Ebola virus as an example, Admera Health developed aptamers against VP35, which were shown to break VP35-NP interaction and inhibit Ebola virus replication in a reconstructed cell systems. Admera Health also showed that aptamers can compete with VP35-dsRNA binding. Taken together, our team has showed that aptamers have great potential in drug development targeting macromolecular interactions.