The unique characteristics and advantages of aptamers are being tested throughout the drug discovery and development process. From the identification of new targets to the use of aptamers as direct therapeutics, conjugates for targeted drug delivery, and agents for enhanced detection and monitoring, aptamers are creating new possibilities in drug development.

Target / Biomarker Discovery

Aptamers can be selected for binding to specific cells of interest without prior identification or isolation of a specific cell surface target.

  • The aptamer selection process is completed with live cells, such as a cancer cell line.
  • Negative selection is used to remove aptamers that bind normal cells or similar cell lines.
  • Aptamers selective for the cell of interest can be used directly in diagnostic or therapeutic applications.
  • Further testing can be performed to identify the aptamer target.

Therapeutic Aptamers

A growing number of aptamers are being considered as direct therapeutic agents. Aptamer therapeutics offer several advantages over antibodies.

  • In vitro aptamer selection and maturation is generally much faster than antibody development.
  • Using Base Pair’s patented multiplex SELEX, aptamers to similar targets can be acquired in a single SELEX procedure, increasing the potential for identification of a successful candidate.
  • Small aptamer size helps facilitate entry into tissues and cells and penetration of the blood-brain barrier, enabling treatment of neurological disorders.
  • Aptamers are generally non-immunogenic, enabling higher doses of drug and reduced side effects.
  • Aptamers are easily conjugated for in vitroand in vivo detection, extended stability, or assisted penetration of cells or the blood-brain barrier.

Targeted Drug Delivery

Aptamer-drug conjugates can be used to deliver drugs to target cells and offer several advantages over antibody-drug conjugates.

  • Directed delivery of drug compounds limits off-target effects. Increased delivery to target cells can lower the required dosage and improve efficacy.
  • Aptamers can be selected to bind with a high degree of specificity to highly similar targets.
  • Aptamer-facilitated binding can sometimes enable entry into cells or across the blood-brain barrier.
  • Aptamers are non-immunogenic.
  • Aptamers can be conjugated without affecting selective binding, enabling modifications to improve stability or labeling to assess aptamer-drug delivery.

Distribution and Dosing Studies

Aptamer labeling and the selection of aptamers to small molecule drugs and drug metabolites creates new possibilities in the study of drug metabolism.

  • Fluorescence labeling can be used to assess distribution of therapeutic aptamers and aptamer-drug conjugates.
  • Aptamers to small molecule drugs can be labeled or complexed for in vivo imaging and assessment of drug distribution.
  • Aptamers to small molecule drugs can be developed for assessment of circulating drug levels via biosensors or aptamer-based assays.
  • Assays or biosensors based on aptamers to drug metabolites can be developed to measure metabolites in urine and monitor drug clearance.

Diagnostics and Trial Candidate Assessment

Aptamers offer a number of advantages in assays for biomarker detection, histological studies, and in vivo imaging.

  • Aptamers are easily selected for binding to proteins, peptides, non-immunogenic small molecules, toxic compounds, or cells of interest.
  • No antibody-related non-specific binding caused by heterophilic antibodies, anti-species antibodies, etc.
  • Thermal stability enables field-based detection in a wide range of climates.
  • Small aptamer size offers enhanced penetration of tumor tissue and access to cell surface targets.
  • Aptamers are non-immunogenic, so there is no interference with processes being studied.
  • Aptamers can be labeled with a wide range of molecules with no loss of selectivity or function
  • Several aptamer modifications are commonly used to delay clearance, extending stability in vivo

Treatment Monitoring with Aptamer-Based Biosensors

Many aptamer-based biosensors are being developed to offer rapid, cost-effective, field-based detection with minimal sample pre-treatment.

  • The ability to select aptamers that bind small molecule drugs and drug metabolites in complex samples makes aptamer-based biosensors a particularly useful platform for the study of pharmacokinetics and drug monitoring
  • Aptamers have been successfully immobilized on a wide range of materials and labeled with a wide range of signaling molecules without loss of selectivity or affinity.
  • The small size of capture aptamers enables binding events to take place close to the biosensor surface for enhanced detection.
  • Aptamer stability and re-folding enables biosensor regeneration.

Aptamer Advantages in Drug Manufacturing

Because aptamers are chemically synthesized, they offer many advantages in terms of manufacturing and quality control.

  • Chemical synthesis is simpler and more cost-effective than bioproduction.
  • Oligonucleotide synthesis offers excellent batch-to-batch reproducibility.
  • Chemical synthesis ensures long-term availability and consistency of product.
  • Elimination of bioproduction reduces regulatory requirements and contamination concerns.