AOC for Therapeutics

The potential therapeutic and diagnostic applications of oligonucleotides (ONs) have attracted great attention in recent years. The capability of ONs to selectively inhibit target genes through antisense and RNA interference mechanisms, without causing unintended side effects has led them to be investigated for various biomedical applications, especially for the treatment of viral diseases and cancer. Armed with rich experience in ON synthesis/modification and antibody conjugation, Creative Biolabs provides personalized antibody-ON conjugates (AOCs) acting as disease therapeutics candidates for worldwide customers.

AOC for Therapeutics

In recent years, bioactive ONs have been combined with monoclonal antibodies (mAbs) to achieve better targeting into desired tissues or cells. As therapeutics, AOCs have been reported as promising gene-silencing anticancer and antiviral agents, enhancing agents for radiotherapy, or tools for studying antibody internalization and metabolism mechanisms.

• Therapeutic AOC Generation

The majority of the therapeutic AOCs were obtained by the recombinant expression of a targeting moiety fused with protamine. Protamine is a validated cationic polypeptide used for the non-covalent complexation of ONs. Several covalent AOCs were generated using chemical approaches, such as the introduction of maleimide and azide residues onto the mAb followed by their reaction with thiol- or strained alkyne modified ONs, respectively. Besides, by using an ON molecule as the payload, mAb can serve as a delivery module to bind drugs, with the subsequent conjugation of the DNA-drug complex to the antibody opening access to targeted therapeutics. Alternatively, to use an ON molecule as the payload, it can serve as a delivery module to bind drugs, with the subsequent conjugation of the DNA-drug complex to the antibody opening access to targeted therapeutics. This approach has been used for the targeted delivery of the drug doxorubicin intercalated into an antibody-conjugated 21-mer DNA and an antibody-conjugated DNA nanostructure (dendritic and tetrahedral).

• Therapeutic Applications of AOCs

There is increasing enthusiasm for developing therapies based on ONs. Engineered mAbs and various antibody fragments have been applied to the generation of AOC therapeutics. For instance, scientists took advantage of the nucleic acid-binding properties of protamine to deliver small interfering RNA (siRNA) via an antibody Fab fragment-protamine fusion protein. The Fab fragment was used to avoid potential side effects from interactions of complement and other molecules with the antibody constant region. Another study reported the development of site-specific AOC for the selective delivery of siRNA to target cells. The AOC was synthesized in good yields by conjugating an aminooxy-derivatized cationic block copolymer to an anti-HER2 Fab or full-length IgG by means of genetically encoded para-acetyl phenylalanine (pAcF). The most relevant examples of the agents reported to date are summarized in Table 1.

Tab. 1 Therapeutic Applications of AOCs. (Dovgan, 2019)

Customized AOC Development Services for Therapeutic Applications

Researchers at Creative Biolabs have focused on enhancing the stability and target specificity of ONs by conjugating them with antibodies or encapsulating/complexing them with polymers or lipid chains to formulate nanoparticles/nanocomplexes/micelles. For ON module, different chemical modification methods have been proposed. Various coupling strategies ensure a satisfactory conjugate. Besides, we have also adopted different strategies in antibody design and engineering to introduce a series of specific and chemically versatile conjugation sites into different antibody formats. If you are interested in our AOCs therapeutics, please don’t hesitate to contact us for more information.

Reference

1. Dovgan, I.; et al. Antibody-oligonucleotide conjugates as therapeutic, imaging, and detection agents. Bioconjugate chemistry. 2019, 30(10), 2483-2501.

For Research Use Only. NOT FOR CLINICAL USE.