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Peptide–Oligonucleotide Conjugation (POC)

Regulatory-ready peptide–oligonucleotide conjugation for DNA, RNA, siRNA, dsDNA, and ASO with explicit orientation control (peptide N-terminus/C-terminus/internal ↔ oligo 5′/3′/strand-specific) plus cleavable & non-cleavable linkers.

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Overview Scale & capability Chemistry & linkers QC & deliverables Release criteria Quality systems Contact

Overview

What is a peptide–oligonucleotide conjugate (POC)?

A peptide–oligonucleotide conjugate (POC) is a construct in which an oligonucleotide (DNA, RNA, siRNA, dsDNA, or ASO) is covalently linked to a peptide to enhance cellular uptake, targeting, stability, or functional delivery. POCs are increasingly used in discovery and development programs where delivery efficiency, orientation control, and linker performance are critical.

Why Bio-Synthesis (CDMO): Bio-Synthesis is a specialized peptide and oligonucleotide CDMO focused on peptide–oligonucleotide conjugation where precision, flexibility, and scalability are essential. We provide strand- and site-specific conjugation, custom chemistry and linker selection, and bench-to-kilo-scale manufacturing within a single organization.

Unlike rigid, high-throughput manufacturing platforms or catalog-driven suppliers, Bio-Synthesis is optimized for programs that require technical iteration, pilot-stage optimization, and evolving specifications. Our scientists work directly with customers to define conjugation orientation (peptide N-terminus, C-terminus, or internal site ↔ oligonucleotide 5′, 3′, or strand-specific attachment), evaluate cleavable versus non-cleavable linker strategies, and align synthetic routes with downstream analytical and regulatory requirements.

Bio-Synthesis supports peptide–oligonucleotide conjugate programs from early bench-scale feasibility through pilot production and kilo-scale manufacturing. Pilot projects are used to optimize conjugation efficiency, impurity control, linker performance, and process robustness—reducing scale-up risk and enabling reproducible, release-ready material.

Peptide–oligonucleotide conjugate schematic showing peptide, linker, and oligonucleotide
POC schematic: peptide + linker + oligonucleotide

With ISO 9001:2015, ISO 13485:2006, GLP, and cGMP-grade options, Bio-Synthesis provides continuity from discovery through regulated manufacturing, minimizing tech-transfer friction and supporting programs advancing toward IND-enabling and clinical supply.

DNA RNA siRNA (sense/antisense) dsDNA (strand A/B) ASO Cleavable & non-cleavable linkers ISO 9001:2015 ISO 13485:2006 GLP cGMP-grade options
Common applications
  • CPP–siRNA / CPP–ASO delivery screening
  • Targeting peptide–ASO/siRNA constructs
  • Cleavable linkers for intracellular payload release
  • Tool compounds for mechanistic studies and assay controls
Why projects slow down
  • Missing orientation (peptide site ↔ oligo end/strand)
  • Unspecified duplex strand (siRNA sense vs antisense; dsDNA strand A/B)
  • Linker requirements not stated (cleavable vs non-cleavable)
  • QC expectations not aligned to use case
When Bio-Synthesis is the right CDMO partner
  • You require strand- or site-specific POC orientation rather than fixed formats
  • Your program needs pilot-stage optimization before large-scale commitment
  • You are evaluating cleavable vs non-cleavable linkers
  • Your specifications are expected to evolve during development
  • You need bench → pilot → kilo continuity under one CDMO
  • Your program must align with ISO, GLP, or cGMP-grade expectations
CDMO partnership model from discovery through pilot and manufacturing

Integrated CDMO support from feasibility through regulated manufacturing

Lead time: Project timelines depend on sequence complexity, conjugation chemistry, linker selection, scale, analytical requirements, and documentation level.

Scale & capability

As a CDMO, Bio-Synthesis supports end-to-end POC programs, from early feasibility through pilot optimization and kilo-scale production. Scale, controls, and documentation are aligned to your development stage.

Stage Typical scale Primary objectives What Bio-Synthesis delivers
Bench / Feasibility mg–g Orientation confirmation, chemistry screening Orientation control (peptide N/C/internal ↔ oligo end/strand), chemistry/linker screening, analytical method development, rapid turnaround.
Pilot / Optimization g–100 g Process robustness, yield & purity improvement Route optimization, conjugation efficiency improvement, cleavable vs non-cleavable linker evaluation, impurity control, scale-up readiness.
Production 100 g–kg Reproducibility, release readiness Kilo-scale manufacturing, validated analytics, defined release criteria, GLP/cGMP-grade options with documentation aligned to program needs.

Exact scale ranges and deliverables are project-dependent. Share your target quantity and timeline to align scope and lead time.

Capabilities

Conjugation formats we support

We can conjugate DNA, RNA, siRNA, dsDNA, and ASO oligos to a peptide at the N-terminus, C-terminus, or internally, with strand-specific control for duplex formats.

Oligonucleotides
  • DNA (ssDNA)
  • RNA (ssRNA)
  • siRNA (sense/antisense)
  • dsDNA (strand A/B specified)
  • ASO (antisense oligo)
Peptide attachment site
  • N-terminus
  • C-terminus
  • Internal (site-defined; specify residue position)

For internal sites, specify position (e.g., Lys8, Cys12) or designated handle.

Oligo attachment site
  • 5′ end
  • 3′ end
  • siRNA strand: sense or antisense
  • dsDNA: strand A or strand B

For duplexes, specify strand + end (e.g., antisense 3′).

Chemistry & linkers

Common conjugation chemistries
  • Click chemistry (SPAAC/CuAAC): selective, modular; SPAAC avoids copper exposure.
  • Thiol–maleimide: rapid coupling to Cys handles (application-dependent stability).
  • Amide coupling (EDC/NHS): robust permanent linkage.
  • Other routes: project-dependent options available upon request.

If you don’t have a preferred chemistry, share your application and we’ll recommend an approach that minimizes heterogeneity and supports your QC targets.

Linkers (cleavable & non-cleavable)
  • Non-cleavable linkers: stable connection for persistent conjugates.
  • Cleavable linkers: enable payload release under defined conditions (application-dependent).
  • PEG / spacers: improve solubility and reduce steric effects.
  • Custom: specify your linker or request a recommendation.

Cleavable linker selection depends on stability needs and intended biology—tell us your workflow and we’ll propose options.

EXAMPLE (explicit orientation): Oligo: siRNA antisense strand, 3′ end Peptide: N-terminus Chemistry: SPAAC click Linker: PEG4 (cleavable or non-cleavable per request)

Quick rule: If you need intracellular release → request a cleavable linker. If you need maximum stability and minimal variables → choose a non-cleavable linker.

QC & deliverables

Fit-for-purpose analytics

POCs can be heterogeneous without the right controls. We align purification and QC to your construct design and requirements.

Typical QC
  • Analytical HPLC/UPLC purity
  • LC–MS or MALDI–MS (as appropriate)
  • PAGE / gel-shift (when applicable)
Deliverables
  • COA and analytical data package (scope-dependent)
  • Project-aligned reporting format
  • Handling / storage guidance as needed
Formats
  • Lyophilized (common)
  • Solution (project-dependent)
  • Salt/buffer preferences as specified

For cleavable linkers, share your planned handling conditions so we can recommend formats that preserve integrity during shipping and use.

Release criteria (examples)

The examples below illustrate common release attributes and test methods used for peptide–oligonucleotide conjugates. Final specifications and test panels are project- and grade-dependent (research, GLP, or cGMP option) and may vary by sequence, linker chemistry (cleavable vs non-cleavable), format (single strand vs duplex), and intended use.

Attribute Typical spec (example) Method
Identity Intact mass within ±5 ppm ESI LC–MS
Purity ≥ 85–98% main peak RP/IP‑RP‑HPLC
Residual solvents Meets ICH Q3C GC
Elemental impurities Meets ICH Q3D ICP‑MS
Sodium content Report / meets target range Ion chromatography or flame photometry
Endotoxin ≤ 0.5 EU/mg (use‑case dependent) LAL
Bioburden USP <61>/<62> acceptance Culture / USP methods
Water content Report or target range Karl Fischer
DNase/RNase Not detected (if applicable) Activity assays

Need a specific panel (e.g., sterility, osmolality, residual reagents, linker cleavage verification)? Include it in your request and we’ll align the testing plan to your release criteria.

Quality systems & grade options

Quality systems
  • ISO 9001:2015
  • ISO 13485:2006
  • GLP options (project-dependent)
  • cGMP-grade options (project-dependent)

Availability and deliverable depth depend on your project requirements.

What to include for regulated workflows
  • Intended use (research, preclinical, clinical support)
  • Requested grade (GLP / cGMP option)
  • Documentation expectations (COA fields, batch records, etc.)
  • Release criteria (purity, identity, residuals, other project needs)

Lead time note: regulated documentation and release requirements can affect schedule—share them early for the fastest plan.

FAQ

More FAQ'sAll FAQ's

CDMO vs CRO vs catalog supplier

Customers evaluating peptide–oligonucleotide conjugation often choose between a CDMO, a CRO, or a catalog supplier. The table below highlights where Bio-Synthesis (as a CDMO) fits.

Capability Bio-Synthesis (CDMO) Typical CRO Catalog supplier
Custom POC design ✔ Full customization (orientation, linker, chemistry) ✔ Limited to study scope ✖ Fixed formats only
Bench → pilot → kilo scale ✔ End-to-end scalability ✖ Bench-scale only ✖ Small catalog quantities
Pilot optimization ✔ Route, yield, purity optimization ✖ Not manufacturing-focused ✖ Not available
Cleavable linker evaluation ✔ Yes ✔ Research-only ✖ No
Release criteria & QC ✔ Defined, program-aligned ✖ Exploratory analytics ✖ Minimal COA
Regulated options (GLP/cGMP) ✔ Available (project-dependent) ✖ Typically not supported ✖ Not supported
Continuity to IND support ✔ Designed for transition ✖ Handoff required ✖ Not applicable

For programs expected to scale or transition toward regulated manufacturing, a CDMO model reduces tech transfer risk and timeline friction.

Contact & quote request

Send your sequences and required orientation (peptide site ↔ oligo end/strand). We’ll respond with a synthesis plan, recommended chemistry/linker options (including cleavable if requested), QC plan, and pricing aligned to your project scope.

Information required to initiate a POC project

To streamline feasibility review and quoting, please include the items below. Clear orientation details (peptide site ↔ oligo end/strand) are essential.

  • Oligo: type (DNA/RNA/siRNA/dsDNA/ASO) and sequence (5′→3′) with modifications
  • Oligo attachment: 5′ or 3′; or strand-specific (siRNA sense/antisense; dsDNA strand A/B)
  • Peptide: sequence (N→C) and attachment site (N-terminus, C-terminus, or internal residue)
  • Sequences: full oligo (5′→3′) + peptide (N→C) with modifications annotated
  • Linker: cleavable vs non-cleavable (PEG/custom if applicable)
  • Target scale & purity: expected quantity and purity requirement
  • QC & grade: requested analytics and research/GLP/cGMP option
  • Intended use: brief application context (especially for cleavable linkers)
Practical notes (to speed feasibility)
  • If your construct is duplex (siRNA/dsDNA), specify strand identity and attachment end.
  • If you need release, request a cleavable linker and share your handling/assay conditions.
  • If you’re unsure about chemistry, write “Recommend”—we’ll propose a robust route and QC strategy.
  • For regulated needs, include your documentation and release expectations early.

Prefer to speak with a chemist? Use the “Speak to a Chemist” button in the hero or contact Bio-Synthesis through your standard support channels.

Lead time depends on project scope (chemistry, linker, purification, analytics, documentation, and scale).

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Recommended reading

The resources below are commonly referenced when establishing analytical strategy, release criteria, and risk-based controls for oligonucleotides and conjugates.

Guidelines & standards

Microbiological methods commonly referenced include USP <61> and <62> (as applicable).

POC & delivery reviews

If you share your modality and linker/chemistry constraints, we can suggest more targeted references.

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 45+ years of delivering high quality, fast and scalable synthetic biology solutions.

Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

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