Insufficient pharmacokinetic characteristics and poor cell uptake are the main obstacles to the successful development of oligonucleotide drugs. Covalent bonding of different ligands, which aim to influence the biodistribution and cellular uptake or target specific tissues, is an attractive possibility to promote therapeutic applications and expand development options. Unlike advanced preparations that are usually composed of multiple reagents and are sensitive to various preparation conditions, oligonucleotide conjugates are defined molecules that can realize structure-based analysis and quality control techniques.
Background of Aptamer-Therapeutic Oligonucleotide Conjugates
With the approval of the first antisense drug and the application of small interfering RNA (siRNA) or splice switch oligonucleotides in advanced clinical trials, significant progress has been made in the field of oligonucleotide therapy. However, the effective delivery of oligonucleotides to their intracellular sites of action is still a major problem.
Like aptamers, several other types of oligonucleotides, including siRNA, microRNA (miRNA), and anti-miRNA (antimiR), are also attractive as therapeutic agents because they regulate the expression of specific cancer targets, including oncogenes that are difficult to tolerate. Because these oligonucleotides function inside the cell, it is important to deliver them efficiently. Since the prostate specific membrane antigen (PSMA) aptamer-siRNA chimera was first reported in 2006, many aptamer-oligonucleotide conjugates have been developed for anti-cancer therapy. Among various therapeutic oligonucleotide conjugates, siRNA-aptamer conjugates are the most popular.
Fig. 1 PSMA aptamer–siRNA conjugates.1
Aptamer-Therapeutic Oligonucleotide Conjugates Development Service
The conjugation of aptamers and therapeutic oligonucleotides can be easily achieved by covalent ligation or complementation (e.g., annealing) to produce aptamer-oligonucleotide conjugates. The significant advantages of this conjugate compared to other methods (such as protein-based systems) are simplicity (one-component conjugate), ease of manufacture, and low immunogenicity. Since nucleic acids are not generally recognized as foreign molecules by the human immune system, the non-specific activation of the immune system induced by aptamer-oligonucleotide conjugates is lower than that of protein-mediated delivery systems.
Among them, aptamer-siRNA conjugates are compatible with natural ribonuclease (Dicer) treatment, resulting in the effective degradation of target mRNA. Similar to siRNA, other types of oligonucleotides (such as miRNA, antimiR, small activated RNA (Sarna) and decoy DNA) can also be successfully coupled to cell-specific aptamers.
Fig.2 Some diagrams of the aptamer-oligonucleotide conjugates. (Hori, 2018)
Since the establishment of systemic evolution of ligands by exponential enrichment (SELEX) technology, many aptamers have been identified and used for target verification and targeted therapy. Based on our complement development for many years, Creative Biolabs proposes various aptamer development services, and is committed to developing more effective and high-quality aptamer-oligonucleotide conjugates from the aspects of targeting specificity, in vivo RNAi effectiveness, easy chemical synthesis and synergistic therapeutic effect.
If you are interested in our service, please contact us for your exclusive solution.
References
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Thiel, Kristina W., and Paloma H. Giangrande. "Intracellular delivery of RNA-based therapeutics using aptamers." Therapeutic delivery 1.6 (2010): 849-861.
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Hori, Shin-ichiro, et al. "Current advances in aptamers for cancer diagnosis and therapy." Cancers 10.1 (2018): 9.
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Questions & Answer
A: The development process typically involves aptamer selection, therapeutic oligonucleotide design, conjugation strategy development, conjugate synthesis, characterization, and in vitro/in vivo evaluation.
A: Various types of therapeutic oligonucleotides, such as siRNAs, antisense oligonucleotides (ASOs), and modified nucleotides, can be conjugated with aptamers.
A: Creative Biolabs employs rigorous quality control measures, including analytical methods and in vitro/in vivo assays, to ensure the quality and functionality of aptamer therapeutic oligonucleotide conjugates.
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