Small Nucleic Acid Drug Conjugation Service

Overview Advantages Workflow Service Case Studies Contact Us

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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

Workflow

Payload design,
synthesis, screening

siRNA/ASO sequence design & synthesis
Modification strategy
Candidate sequence screening

Carrier design,
synthesis, screening

Antibody design & synthesis (scFv, mAb, etc.)
Peptide design & synthesis (cell-penetrating peptides, etc.)
Protein design & synthesis (KLH, BSA*, etc.)

Conjugation and product identification

Antibody/peptide/protein-oligo conjugates
Degradable/non-degradable linkers, DAR1 or random conjugates (DAR>1)
Purity, DAR, and physicochemical property testing

In vitro/In vivo efficacy
and PD/PK

In vitro: knockdown efficiency, IC₅₀, stability, off-target effects, toxicity
In vivo: knockdown efficiency, PD/PK

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

Service

Service Type	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
Production Time	From 2 weeks

Multiple conjugation solutions available:

AOC: Random Lys/Cys conjugation, N-terminal specific conjugation, and more.
POC: 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.
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 oligo@genscript.com.

Case Studies

DAR1 Conjugation: precisely defined conjugates with higher knockdown efficiency and stability
Multiple detection methods are used to identify the DAR1 conjugation product
Observed MW matches the theoretical MW.

CE-SDS shows LC, HC, and HC+1, confirming DAR1.

DE-Glycosylation Mass spectrometry

CE-SDS

SDS-PAGE shows LC, HC, and HC+1, confirming DAR1.

SDS-PAGE
SEC confirms intact conjugate; higher MW shifts peak left.

AOC MW exceeds that of the antibody and oligo.

AOC A260/220 ratio falls between that of the antibody and oligo.

Size Exclusion Chromatography (SEC)
At in vitro level, DAR1 conjugate has high silencing efficiency.

In mice, DAR1 conjugate shows higher serum concentration and stability.
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 conjugates (up to 99%!) available
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

HPLC

MS

MS
AOC shows superior uptake and precise gene silencing
Superior cellular uptake and targeted binding
- The AOC conjugate maintains comparable internalization efficiency to the native antibody, ensuring effective cellular entry (left image)
- It preserves full antigen-binding capability, demonstrating precise targeting (right image)
Precise gene silencing capability:
- 50% silencing efficiency in cells expressing the target receptor (left image)
- No off-target effects in receptor-negative cells, confirming specificity (right image)