Small Nucleic Acid Drug Conjugation Service

Overview Advantages Workflow Service Case Studies Contact Us

Home » Oligo Synthesis Applications » Small Nucleic Acid Drug Development Services » Small Nucleic Acid Drug Conjugation Service

Overview

Targeted delivery enhances the safety and efficacy of small nucleic acid drug. By conjugating siRNA or ASO with targeting molecules- such as antibodies or peptides- cellular uptake, stability, and bioavailability are improved, while immunogenicity and toxicity are reduced.

GenScript offers customized covalent conjugation services for nucleic acids, supporting diverse needs such as Antibody-Oligo Conjugates (AOCs) and Peptide-Oligo Conjugates (POCs) development. Our high-quality conjugates ensure precise delivery and effective gene silencing, accelerating your drug development timeline.

Advantages

Supports Diverse
Conjugation Needs

AOC/POC, random or site-specific conjugation
Customizable conjugation sites, linkers, and DAR values

High Quality Ensures
Precise Knockdown

High purity and batch-to-batch consistency
Proven targeting and potent gene silencing

One-Stop Synthesis,
Conjugation & Validation

Oligo/peptide synthesis, protein/antibody production
Full characterization and efficacy testing

Oligo Synthesis

One-Stop Solution for All Your Oligo Conjugation Needs

GenScript’s end-to-end oligo conjugation solution supports every stage of development—from discovery and design to payload production, conjugation and characterization, in vitro and in vivo verification, and manufacturing—helping accelerate your path from concept to candidate.

Design &
Production

Oligo

siRNA/ASO
Primers/probes
>200 modifications
nmol-mmol level

Antibody

scFv/mAb/VHH

Protein

KLH/BSA/Streptavidin

Peptide

Cell penetrating peptide (CPP)

Conjugation &
Characterization

Conjugation

Antibody-oligo conjugation (AOC)
Peptide-oligo conjugation (POC)
Protein-oligo conjugation (POC)
Antibody-peptide conjugation (APC)
DAR1 or random conjugates (DAR >1)

Linker

Linker toolbox
Custom process
Degradable/non-degradable linkers

Characterization

Purity, composition, DAR, Physicochemical analysis

In-vitro & in-vivo
Verification

Biological

In-vitro KD efficiency
Binding affinity
Internalization
IC50
Cell killing

Pharmacological

In-vivo efficacy
PK/PD
Initial toxicology

Manufacturing

Non-GMP grade

AOC 100 mg level
POC mg level
APC mg level
CMC development

* GenScript supports oligo conjugation to proteins like KLH and BSA to enhance in vivo half-life and immunogenicity for antibody generation.

Service

	AOC	POC
Payload	RNA/DNA Oligo: 3-60 nt	RNA/DNA Oligo: 3-130 nt
Carrier	Antibody/Protein:＜1000 kDa	Peptide: 1~40 AA
QC	Purity (SEC), conjugate product ratio (SDS-PAGE) - default MS，IEX，CE-SDS, etc. - optional	Purity (RP-HPLC), molecular weight (MS) - default
Quantity	1-100 mg. For other quantities, please inquire here	0.2-20 mg. For other quantities, please inquire here
Method	Random Lys/Cys conjugation, N-terminal specific conjugation, and more	Copper-free or copper-catalyzed click chemistry, Michael addition, and bispecific linkers (e.g., SMCC, EMCS, SPDP). Recommendation: SMCC for non-degradable linkers; SPDP for degradable linkers
Production Time	From 2 weeks

Multiple conjugation solutions available:

Conjugation Options: DAR1 or random conjugate product (DAR>1), with flexible conjugation at any position on the nucleic acid. Supports antibody-oligo, peptide-oligo, and antibody-peptide formats.
Conjugation Linkers:
- Degradable: SPDP, DBCO-Val-Cit-PAB-PNP, MC-Val-Cit-PAB-PNP, etc.
- Non-degradable: SMCC, EMCS, N3-PEG4-NHS, DBCO-PEG4-NHS, etc.

How to order: Download the quote form and fill in the necessary information for your request. Send the quote form to your Technical Account Manager or to [email protected].

Case Studies

Supports multiple conjugation sites and various linkers
Peptides conjugated to either strand of siRNA, both with product purity ≥90%.

Peptide conjugated to siRNA sense strand

Peptide conjugated to siRNA antisense strand

Peptides conjugated at multiple oligo positions.

5’ End Conjugation

Mid-Oligo Conjugation

3’ End Conjugation
Conjugates with varied strategies and DAR values deliver robust gene knockdown:

N-terminal site-specific conjugation (SS)

Lysine random conjugation (Lys)

Cysteine random conjugation (Cys)
High-purity oligo conjugates generated across diverse biomolecule scaffolds
Antibody-oligo conjugate with up to 99% purity
- Oligo: 21 nt + 23 nt siRNA / Antibody: Cetuximab
- Denaturing PAGE：LC (light chain), HC (heavy chain), and HC+1 (heavy chain + 1 oligo) oligo confirm DAR1.
- Agarose/SEC：intact AOC; post-purification purity > pre-purification reaction mixture (Mix).
Denaturing PAGE

Agarose

Size-Exclusion Chromatography (SEC)
Protein-oligo conjugate

Protein：Maltose-binding protein (MBP)

Oligo：16 nt DNA
Peptide-oligo conjugate with up to 98% purity

Peptide：14-aa

Oligo：41 nt DNA
Denaturing PAGE

MS

HPLC

MS
AOC with mAb achieved 94% purity of DAR1 product characterized by multi-orthogonal analysis
Ion Exchange Chromatography

DE-Glycosylation Mass Spectrometry

Size-Exclusion Chromatography

CE-SDS

SDS-PAGE
DAR1 AOC was generated from a monoclonal antibody through partial reduction and oligonucleotide conjugation.

IEX purification enriched the target DAR1 product from the crude reaction mixture.
MS, SEC, CE-SDS, and SDS-PAGE provided multi-orthogonal confirmation of product identity and quality.

The purified DAR1 AOC reached 94.23% purity.
DAR1 AOC with VHH reached 95% purity by site-specific method
IEX Analysis for Reaction Mixture

Reaction mixture profiling showed formation of the target AOC species.
IEX Analysis for AOC

Purified VHH AOC reached 95.86% purity by IEX analysis.
Native MS Analysis for AOC

Native MS confirmed the molecular identity of the VHH-siRNA conjugate.
DAR1 AOC with bispecific antibody attained 99% purity
IEX Analysis for Reaction Mixture

Optimized conditions improved DAR1 conversion from 42.5% to 75.8% in the reaction mixture.
SDS-PAGE Analysis for AOC

SDS-PAGE confirmed successful AOC formation, with DAR1 conversion rate reaching 81.26%.
IEX Analysis for AOC

IEX analysis confirmed 99.93% purity of the purified bispecific antibody DAR1 AOC.
Precisely random & site-specific antibody-peptide conjugation
Random Conjugation with Reduced Cys

Migration shift on SDS-PAGE indicate the success of peptide labeling.

Successful multiple labeling was observed from mass spectrometry analysis.
Thiomab Based Conjugation

Migration shift on SDS-PAGE indicates the success of peptide labeling.

Successful single labeling was observed from mass spectrometry analysis.
Bioanalysis of AOC (DAR1) demonstrate superior functionalities

The AOC conjugate maintains comparable internalization efficiency to the native antibody, ensuring effective cellular entry

At in vitro level, DAR1 conjugate has higher silencing efficiency
(Tfr1 antibody conjugated with DMPK siRNA)

The AOC conjugate preserves full antigen-binding capability, demonstrating precise targeting

In mice, DAR1 conjugate shows slower metabolizing rate
(Tfr1 antibody conjugated with DMPK siRNA)