AOC Development and Production

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Oligonucleotide-based gene therapy has rapidly advanced due to its unique advantages in regulating gene expression, offering new hope for disease treatment. Despite challenges like high molecular weight, hydrophilicity, and low stability limiting cell membrane penetration, delivery systems like LNP and GalNAc have been developed, although they primarily target the liver. An emerging strategy for delivering oligonucleotides beyond the liver is via Antibody-Oligonucleotide Conjugates (AOCs), combining monoclonal antibodies with oligonucleotides to leverage ADC advances for enhanced targeting.

What are AOCs?

AOCs integrate three critical components: a targeting antibody that binds to tissue-specific receptors (such as TfR1 for CNS delivery), a carefully engineered linker that balances oligonucleotide release efficiency with stability, and therapeutic oligonucleotides (including siRNA, ASO, or PMO) with chemical modifications for enhanced stability.

Figure 1 illustrates the structural components of an AOC. Figure 1. Structure-activity relationships of antibody-oligonucleotide conjugates.

The research and development of AOCs are advancing rapidly. Currently, Avidity has three AOC drugs in clinical research, with AOC1001 being the first to enter clinical trials, primarily targeting type 1 Myotonic Dystrophy (DM1) and demonstrating significant efficacy in early trials. Globally, over 30 AOC projects have progressed to clinical stages, covering a range of therapeutic areas from cancer to rare diseases. This not only highlights the broad application potential of AOCs but also ignites enthusiasm in the investment market.

Drug	Sponsor	Antibody	Payload	Disease
AOC1001	Avidity	TfR1 (mAb)	DMPK siRNA	DM1
AOC1044	Avidity	TfR1 (mAb)	Exon−44-skipping PMO	DMD
AOC1020	Avidity	TfR1 (mAb)	DUX4 siRNA	FSHD
DYNE−251	Dyne	TfR1 (Fab)	Exon−51-skipping PMO	DMD
DYNE−101	Dyne	TfR1 (Fab)	DMPK ASO	DM1
DYNE−301	Dyne	TfR1 (Fab)	DUX4 ASO	FSHD
TAC−001	Tallac	CD22 (mAb)	CpG (TLR9 agonist)	Cancer
TAC−003	Tallac	Nectin−4 (mAb)	CpG (TLR9 agonist)	Cancer
ALTA−002	Tallac/ALX Oncology	SIRPα (mAb)	CpG (TLR9 agonist)	Cancer

Despite the vast market potential of AOC drugs, their development faces challenges, particularly in improving the conjugation and purification processes, which remain critical issues to be addressed. Additionally, ensuring drug stability, enhancing efficacy, reducing side effects, and establishing a rational dosing sequence to prevent cross-resistance and strengthen market regulation are imperative tasks for the industry to tackle.

Creative Biogene's Comprehensive AOC Development Solutions

For more than ten years, Creative Biogene has been at the forefront of discovering and optimizing nucleic acid-based drugs. By harnessing cutting-edge innovation and deep technical expertise, we combine antibody technology, CRISPR, AI, and other platform strengths to boost the efficiency and success rate of AOC drug development. Our tailored solutions enable clients to quickly and effectively enter the rapidly growing field of AOC-based therapeutics.

Antibody Development & Optimization

Antibody Screening

We select high-affinity antibodies using advanced phage display and B-cell screening techniques, delivering candidates with optimal target binding (TfR1, ASGPR, CD19) and minimal immunogenicity.

Antibody Engineering

Our Fc domain modification and fragmentation services (Fab, scFv) enhance conjugation efficiency while optimizing immunogenicity profiles and tissue penetration capabilities.

Sequence Design

Combining computational approaches with medicinal chemistry, we design highly specific oligonucleotides (siRNA, ASO, PMO) with strategic chemical modifications (2'-OMe, PS backbone) for improved stability and efficacy.

Scale-up Synthesis

We offer research to GMP-grade oligonucleotide synthesis with exceptional purity and low endotoxin levels, supporting seamless development progression.

Precise Conjugation Technology

Advanced Conjugation Technologies

Our site-specific approaches—thiol-maleimide, non-natural amino acids, and glycosylation-based methods—produce uniform, stable AOCs while our optimized traditional methods ensure scalable manufacturing.

Versatility

We accommodate diverse antibody formats and oligonucleotide designs with customizable conjugation parameters to match your requirements.

Customized Conjugation Solutions

We develop tailored strategies with optimized linker chemistry (acid-sensitive).

Rigorous Quality Control & Validation

We employ techniques like High-Performance Liquid Chromatography (HPLC), Mass Spectrometry (MS), Nuclear Magnetic Resonance (NMR), and functional activity assays to ensure product purity (≥95%), stability, and targeting specificity. All processes comply with international standards, including the ISO 13485 quality management system, ensuring batch-to-batch consistency and product reproducibility.

Service Workflow

Requirement Communication: We engage with clients to clarify target selection, antibody types, and oligonucleotide sequence needs.
Solution Design: Based on the client's needs, we provide a detailed feasibility analysis and customized development plan, along with a comprehensive quotation.
Process Development & Scale-up: We complete small-scale optimization according to the customized plan and scale up to pilot production for conjugate delivery.
Quality Control & Validation: We ensure product quality with detailed analysis reports, covering purity, activity, stability, and efficacy data.
Delivery & Support: We offer GMP production, technical transfer support, and clinical submission guidance based on project needs.

Contact Us

Through our integrated approach and advanced technologies, we support your AOC development from initial concept through clinical trials and commercial production. Contact us to accelerate your innovative therapeutic development to new heights.

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