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The secrets of single-stranded DNA or RNA: Why do they make excellent drug carriers?
With the rapid development of biomedical research, scientists are constantly looking for novel drug delivery systems. The potential of single-stranded DNA and RNA as drug carriers has received increasing attention because they can not only specifically recognize target molecules but also improve the accuracy and safety of treatment.
Single-stranded nucleic acid molecules, especially aptamers, have become important players in biosensing and therapeutic delivery.
The rise of SELEX technology
Since it was first proposed in 1990, the Systematic Evolutionary Exponential Enrichment of Ligands (SELEX) technology has developed a variety of variants and applications and has become an important method for biomolecule screening. This technique is characterized by the generation of aptamers through an iterative process to select single-stranded RNA or DNA that can bind tightly to a specific target, such as a protein or small molecule.
Generation of single-stranded oligonucleotide library
The first step in SELEX is the synthesis of a library of randomly generated oligonucleotide sequences. These sequences are generated at a fixed length and bounded by constant 5' and 3' ends to allow for polymerase chain reaction (PCR) amplification. As researchers continue to explore this process, scientists have discovered that the use of chemically modified nucleotides can significantly improve the stability and recognition capabilities of aptamers.
The use of chemically modified nucleotides expands the potential applications of aptamers, including biosensing, therapy, and diagnosis.
Incubation of target molecules
Before the single-stranded oligonucleotide library to be generated is bound to the target, it usually needs to undergo a heating and cooling process in order to form thermodynamically stable secondary and tertiary structures. The key in this process is how to effectively isolate and elute unbound nucleic acids to accurately obtain specifically bound sequences.
Elution and amplification of binding sequences
After completing the incubation, researchers need to use denaturing conditions to elute the bound sequence. This usually involves increasing the temperature of the solution or adding a denaturant such as urea. These eluted sequences are then subjected to reverse transcription or direct amplification to generate the initial input for the next round of selection.
Effective nucleic acid amplification methods and clean-up steps are important guarantees for successful SELEX.
Specific applications and cases
Many studies have shown that SELEX technology can successfully generate high-affinity aptamers for various small molecules and proteins. For example, aptamers targeting tumor cells and tumor ex vivo microcapsules have been developed and have shown promising therapeutic prospects.
Potential for chemically modifying nucleotides
Recently, the scientific community's interest in chemically modified nucleotides has attracted everyone's attention. These nucleotides can provide more advantages for the selection of aptamers, including stability, resistance to nucleases, enhanced resistance to specific The combination of goals, etc.
SELEX variations and alternatives
With the further development of SELEX, new technologies such as FRELEX have emerged, which can perform aptamer selection without the need for fixed targets or oligonucleotide libraries. This is particularly effective for selecting aptamers with small molecules or unknown targets.
Clinical application prospects
Aptamers with high affinity have shown potential in clinical treatments, such as Macugen, which has been approved by the FDA for the treatment of macular degeneration. These aptamers can be used not only for targeted therapy but also in diagnostic technology.
Conclusion
In short, single-stranded DNA and RNA show great potential in drug delivery and therapy due to their unique structures and functions. As technology continues to advance, can we fully tap and utilize the potential of these nucleic acids to address various medical challenges in the future?
