Aptamer-Drug Conjugation (ApDC)

As a leading service provider focused on drug development, BOC Sciences has been supporting customers at the forefront of drug conjugation. Building drug conjugates facilitates the selective delivery of toxic therapeutic cargos to diseased cells. Among them, nucleic acid aptamers are one of the delivery systems that have received the most attention. We provide aptamer drug conjugation services to meet your unique project needs.

Aptamer Conjugation

Because they are subject to nuclease degradation and their small size makes them susceptible to renal filtration, aptamers usually require chemical modification. Aptamers are short, single-stranded DNA or RNA oligonucleotides whose biological stability and binding affinity can be enhanced by introducing modifications to their sugar units, nucleobases, or phosphate backbones. Common methods for aptamer conjugation include thiol-maleimide, carbodiimide, oxidative coupling, avidin-biotin coupling, and click chemistry.

Aptamers have been used in drug delivery systems carrying various types of drug cargos. BOC Sciences has the expertise in aptamer conjugation, including conjugating aptamers to therapeutic agents creates aptamer drug conjugates (ApDCs), enabling the precise delivery of drugs to specific cells or tissues and minimizing off-target effects.

What is an Aptamer?

Nucleic acid aptamers, also known as chemical antibodies, has a unique three-dimensional structure allowing it to bind to a molecular target through secondary or tertiary conformation, served as potential drug-delivery vehicles. The targets of aptamers range from small molecules and proteins to intact cells.

Advantages of aptamers served as targeting ligands:

• Small size
• High chemical stability
• Facile chemical modification
• Low immunogenicity
• Rapid tissue penetration

Table 1. Examples of aptamers selected with potential for targeted therapy (Liu, 2022)

The process of developing aptamers is known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). During SELEX, a random pool of nucleic acid sequences is exposed to the target molecule, and those sequences that bind to the target are selectively enriched through iterative rounds of selection, amplification, and isolation. This iterative process leads to the identification of specific aptamer sequences that exhibit high affinity and specificity for the target.

Aptamer Drug Conjugate

In the context of drug development, ApDCs have been developed for targeted therapy. An ApDC typically consists of three molecular parts: a ligand (aptamer), a linker, and a warhead (drug). In these conjugates, aptamers specifically recognize diseases-associated biomarkers to deliver conjugated drugs to target cells or/and tissues. The chemical stability and simplicity of chemical modification of aptamers allow these to be easily combined with many warheads, such as chemotherapeutics, nucleic acids, proteins, photosensitizers, etc.

Fig 1. Aptamer conjugation with drug, antibody, or RNA (Chen, 2022)

Our Services for Aptamer Drug Conjugates

• SELEX method for screening aptamers.
• Chemical modification or insertion of drug molecules into DNA structures for drug aptamer conjugation.
• Adjustment for payload/drug load (proportion of drug part carried by a single aptamer drug conjugate unit).

Table 2. Examples of aptamer-drug conjugates

What are Aptamer Drug Conjugates Used For?

Combined with aptamer, the diagnosis and treatment of diseases can effectively avoid the problems of low diagnostic sensitivity in vivo, large side effects of drugs, difficult tumor monitoring and so on. With the continuous development of aptamers, ApDC with different target sites are more and more widely used. ApDCs are used for targeting drug delivery in chemotherapy, gene therapy, immunotherapy, photodynamic therapy and photothermal therapy for the treatment of various cancers such as liver, ovarian, skin, prostate, breast, pancreatic and anaplastic thyroid cancers, as well as acquired immunodeficiency syndrome. In addition, aptamer conjugates can be extended to other types of metal-organic framework (MOF) nanomaterials, and conjugates with targeted therapeutic and imaging capabilities can be developed for cancer cell detection and imaging.

Our Advantages

• Deep development experience in oligonucleotide synthesis and aptamer screening
• Various conjugation methods through chemical modification or molecular engineering
• Personnel and kit specialized in the development, manufacturing and testing of aptamer drug conjugates
• Customized aptamer modification and conjugation