RNA Aptamers: Targeted Therapeutics and Diagnostics

RNA aptamers are single-stranded RNA molecules that fold into specific shapes. These shapes allow them to bind to other molecules with high accuracy, like a key fitting into a lock. This specific binding makes RNA aptamers useful for developing new treatments and diagnostic tests.

Development of RNA Aptamers: SELEX

Scientists develop RNA aptamers using a method called SELEX, which stands for Systematic Evolution of Ligands by Exponential Enrichment. SELEX starts with a large pool of random RNA sequences. These sequences are then exposed to the target molecule, and any sequences that bind well to the target are isolated and copied. This process is repeated multiple times, resulting in a collection of RNA aptamers that bind very tightly to the target molecule.

Schematic illustration of SELEX protocol for aptamer identification. SELEX consists of a very defined iterative procedure, i.e. library preparation, target and library incubation, bound/unbound sequence separation, elution of target bound sequences, PCR amplification, and single-stranded DNA separation (for DNA aptamer) or transcription (for RNA aptamer). Differing from traditional antibodies, the development of aptamers is performed in vitro.

Advantages of RNA Aptamers

RNA aptamers offer several advantages over traditional molecules used in medicine, such as antibodies:

  • Target variety: Aptamers can bind to a wide range of molecules, including small molecules, proteins, and even whole cells.
  • Stability: They are stable under a variety of conditions, including different temperatures and exposure to enzymes that can break down other molecules.
  • Small size: Their small size allows them to enter tissues more easily and may reduce the chance of side effects compared to antibodies.
  • Modifiability: Scientists can modify RNA aptamers to improve their performance in the body or attach labels to them for detection purposes.

Important advantages of aptamers over antibodies in clinical applicability and industrialization.

RNA Aptamers in Therapeutics

Due to their specific binding, RNA aptamers are being explored for use in new therapeutic approaches:

  • Drug delivery: Aptamers can be linked to drugs or nanoparticles and then delivered to specific diseased cells, reducing the impact on healthy cells.
  • Anticoagulants: Aptamers that target certain clotting factors may be used as anticoagulants with potentially fewer bleeding risks than current medications.
  • Cancer treatment: Aptamers could target cancer cells or molecules that help tumors grow, offering new options for cancer therapy.

The SELEX process. An initial DNA library is transcribed into RNA and the aptamers that bind to cells or beads with no target protein are eliminated. The remaining aptamers are applied to cells or beads with target protein and the bound aptamers are retrieved, amplified, and the SELEX process repeats.

RNA Aptamers in Diagnostics

The high accuracy of aptamers makes them valuable tools for diagnostics:

  • Biosensors: Aptamers can be incorporated into biosensors to detect disease markers, pathogens, or toxins with high sensitivity.
  • Imaging: Aptamers linked to imaging agents can be used to image specific tissues or disease markers inside the body.
  • Early disease detection: Aptamers may help detect diseases earlier by identifying small changes in the levels of certain molecules.

Main characteristics and functionalities of nucleic acid aptamers to overcome various limitations of conventional biosensors. Specific base pairing (top, left) folds the sequence-controllable biopolymers into thermodynamically-favored 3D nanostructures that enable molecular recognition (top, middle). The synthetic aptamers have unique features that can facilitate the development of next-generation biosensors (top, right). Here, we review technical advances in the development of aptamer-based biosensors, such as increases in sensitivity and selectivity, and actualization of newly emerging real-time and in-field detection applications, along with aptameric biosensors’ interesting properties, such as amenability to modularization (bottom).

Conclusion

RNA aptamers are a promising new approach for targeted therapeutics and diagnostics. Their unique properties offer significant potential to improve healthcare. As research continues, we can expect to see more aptamer-based therapies and diagnostic tools developed, leading to better treatment outcomes for patients.

Future Directions:

The field of RNA aptamers is rapidly advancing. Future research will focus on improving aptamer stability and production methods, developing better delivery methods for therapeutic applications, and creating new diagnostic platforms based on aptamers.

Learn more about advances in SELEX technologies for aptamers:

 


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RNA Aptamers: Targeted Therapeutics and Diagnostics
Gen store May 27, 2024
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