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Mopholino Oligonucleotide

Precise, Reliable Gene Expression Control

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Custom Morpholino (PMO) Synthesis

Stable, charge‑neutral antisense oligos tailored for splice‑ and translation‑blocking in cells and embryos.

Overview Thiomorpholino Technology Synthesis Options Modifications Conjugations & Delivery QC How to Order FAQ Contact
ISO 9001:2015 / ISO 13485:2016 45+ Years of Expertise U.S.A. Facilities-Texas GLP/GMP-Aligned

Overview

Morpholino (PMO) antisense oligonucleotides replace the ribose–phosphate backbone with morpholine rings linked by phosphorodiamidate bonds, yielding a charge‑neutral, nuclease‑resistant chemistry. PMOs act by steric blocking—they do not recruit RNase H—making them ideal for splice modulation and translation blocking.

Bio‑Synthesis provides end‑to‑end custom PMO synthesis with labeling, linkers, and delivery enhancers, supported by rigorous QC documentation and optional advanced testing.

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At-a-Glance

  • Length: 10–40 bases (20–25 typical)
  • Purification: HPLC standard; PAGE optional
  • Labeling: 5′/3′ end, internal via spacers
  • Delivery enhancers: CPPs, PEGs, lipids (on request)
  • QC: MS (MALDI‑TOF/ESI), analytical HPLC
  • Scales: 1 mg to gram quantities

Key Advantages

Exceptional Stability

Highly resistant to nucleases and proteases; robust in serum and in vivo.

Charge‑Neutral Backbone

Minimizes non‑specific interactions and enables efficient hybridization under physiological conditions.

RNase H‑Independent

Steric‑block mechanism suits splice correction and translation start‑site blocking.

Applications

  • Splice‑switching assays
  • Translation‑blocking (AUG/start site)
  • Gene function studies and target validation
  • Embryo microinjection (e.g., zebrafish, Xenopus)
  • Cell culture delivery with uptake enhancers
  • Allele‑/SNP‑discriminating designs (research)
  • Probe labeling for imaging and detection
  • PMO chimeras and targeted delivery constructs
  • Preclinical tool compounds (RUO/GLP; cGMP on request)

Custom Synthesis Options

Parameter Options
Length 10–40 bases (20–25 recommended for most targets)
Purification HPLC (standard); PAGE optional
Label Positions 5′, 3′, internal via spacer/linker
Delivery Format Lyophilized; buffer on request
Scales 1 mg to gram quantities; custom bulk on request
QC Package MS (MALDI‑TOF/ESI), analytical HPLC; optional Tm/hybridization

Popular Modifications & Linkers

Category Examples Common Uses
Fluorescent Dyes FAM, HEX, TET, TAMRA, ROX, Cy3/Cy5, ATTO, Alexa Fluor Imaging, uptake studies, localization
Affinity Tags Biotin (short/long spacer), Digoxigenin Capture, pull‑downs, detection
Reactive Handles Amine, Thiol, Azide/Alkyne, Maleimide Protein/peptide coupling; click chemistry
Spacers / PEG Ahx, AEEA, miniPEG, PEG(n), C6/C12 alkyl Improve solubility; reduce sterics
Quenchers (optional) BHQ‑1/2/3, Iowa Black Quenched probe designs
Cleavables (on request) Disulfide, photocleavable spacers Triggered release & controlled activation

Closure & Ligation Methods

Type Linker Chemistry Applications
CPP–PMO (cell‑penetrating peptides) Maleimide–thiol, amide coupling, click (CuAAC/SPAAC) Enhanced uptake in cells/tissues
Lipid‑PMO Cholesterol/stearyl via heterobifunctional linkers Membrane interaction & delivery
Protein/Oligo–PMO PEGylated linkers, azide/alkyne, SMCC/maleimide‑NHS Targeted delivery & hybrid constructs
We offer much more than listed! - get in touch   
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Quality Assurance

  • Mass spectrometry for molecular weight confirmation
  • Analytical HPLC chromatogram and purity report
  • Optional: UV‑melting (Tm), hybridization/functional assays
  • Documentation suitable for RUO; GLP/cGMP support upon request

Typical Turnaround

Standard labeled PMOs: 2–3 weeks from order confirmation. Complex chimeras or peptide conjugations may require additional time.

Lead time depends on sequence and modification complexity; rush options may be available.

How to Order

  1. Provide your target and PMO sequence concept (we can assist with design).
  2. Select labels, linkers, and delivery enhancers.
  3. Choose scale, purification, and optional tests.
  4. Receive a same‑day quote and timeline.

Include organism/cell line and delivery method (e.g., microinjection, electroporation, CPP) if known.

Design Checklist

  • Splice‑ vs translation‑blocking objective
  • Target exon/intron boundaries or start‑site context
  • Length (20–25 typical) and GC balance
  • Controls (scrambled or 5‑mismatch) if required

Morpholino (PMO) & Thiomorpholino (TMO) Technology & Benefits

Overview: Morpholino (PMO) and Thiomorpholino (TMO) oligonucleotides are single-stranded antisense chemistries that bind RNA with high specificity to sterically block processes such as translation initiation or pre-mRNA splicing. Both are engineered for exceptional nuclease resistance and reliable performance in complex biological matrices.

Morpholino (PMO) — Technology

  • Backbone: Neutral phosphorodiamidate linkages with a morpholine ring sugar mimic (no natural phosphate charge).
  • Mechanism: Steric block—does not recruit RNase H; ideal for splice modulation and translation blocking.
  • Stability: Highly resistant to nucleases and proteases; low non-specific protein binding due to neutral charge.
  • Design: Typical length 18–25 nt; target accessible RNA regions (splice junctions, UTRs, start codon vicinity).
  • Delivery: Often paired with peptide/ligand conjugates or formulations to enhance uptake (e.g., CPPs, lipids, nanoparticles).

Thiomorpholino (TMO) — Technology

  • Chemistry: Sulfur-containing morpholino frameworks introduce tunable physicochemical properties (charge/hydrophobicity) while preserving steric-block function.
  • Mechanism: Steric block (non-RNase H), analogous to PMO, for splicing modulation and translation interference.
  • Stability: Retains strong nuclease resistance; backbone/topology designed for durability.
  • Design: Similar lengths (≈15–25 nt). Charge-balanced designs can improve uptake; still compatible with conjugation strategies.
  • Compatibility: Supports labels (dyes, biotin), spacers (AEEA/PEG), and targeting ligands for tailored applications.

PMO Benefits

  • Exceptional stability and long functional lifetime in serum.
  • Precise splice control (exon skipping/inclusion) and translational blockade.
  • Low intrinsic immunostimulation versus double-stranded modalities.
  • Clean analytics and reproducible, fully synthetic manufacturing.

TMO Benefits

  • Programmable uptake/potency via sulfur-enabled tuning and/or conjugation.
  • High specificity with robust mismatch discrimination (sequence-defined recognition).
  • Versatility: Splice modulation, translational block, and research-grade stabilization strategies.
  • Scalable synthesis with standard HPLC/MS QC and optional functional assays.

Design Notes (Practical)

  • Target accessible RNA (splice junctions, weak secondary structure regions).
  • Use length 18–25 nt as a starting range; refine by predicted Tm and accessibility.
  • Consider conjugation (peptides, GalNAc, lipids) to improve cellular uptake and tissue targeting.
  • Include controls (scramble/mismatch) and confirm on-target effects by RT-PCR or protein readouts.

Benefits at a Glance

  • High stability in biologic fluids (nuclease-resistant backbones).
  • Precise RNA modulation without cleavage (steric-block mechanism).
  • Low background binding (PMO neutrality) and tunable uptake (TMO/conjugates).
  • Fully synthetic and reproducible from RUO to GLP/cGMP.

Performance depends on sequence, accessibility, and delivery. We can optimize chemistry and conjugation for your target tissue and assay format.

Use Case Why PMO/TMO Help Typical Setup
Splice modulation (exon skip/inclusion) Direct, cleavage-free control of pre-mRNA processing PMO or TMO (18–25 nt) targeting splice sites; optional peptide/ligand conjugate
Translation blocking Prevents initiation or ribosome progression PMO/TMO to start codon/5′ UTR; fluorescent tag for tracking if needed
Hard-to-reach tissues Enhanced internalization with conjugates PMO/TMO + CPP, lipid, or receptor ligand; HPLC-purified; MS-confirmed
Imaging & trafficking studies Stable probes with low background binding Dye-labeled PMO/TMO with PEG spacer; live-cell or in vivo imaging
Optimize My PMO/TMO Design

FAQ

How do Morpholinos work?
PMOs bind their complementary RNA by base pairing and sterically block the ribosome (translation‑blocking) or spliceosome (splice‑switching). They do not recruit RNase H and therefore do not cleave the RNA.
What sequence length is recommended?
Most designs are 20–25 bases. Shorter (~18–20) can increase specificity for clamping; longer may be used for challenging targets. We can optimize based on your target and delivery method.
Design tips for splice‑blocking vs translation‑blocking?
For splice modulation, target the exon–intron junction (donor/acceptor) or regulatory elements. For translation blocking, target the AUG/start site and flanking UTR. Avoid long homopolymer runs and extreme GC.
What delivery methods are supported?
Common options include microinjection (embryos), electroporation, CPP conjugation (arginine/guanidinium‑rich peptides), and lipid conjugation. We can recommend strategies for your model.
What QC is included?
Each lot includes MS identity confirmation and an analytical HPLC chromatogram. Additional functional/hybridization tests can be added.
How should PMOs be stored?
Store lyophilized PMOs at 4 °C (short‑term) or −20 °C (long‑term). In solution, use nuclease‑free water or buffer (pH 7–8), aliquot, and keep at −20 °C to minimize freeze‑thaw.
Do you offer GLP/cGMP production?
Yes. We support RUO through GLP and cGMP with appropriate documentation and QA oversight. Include regulatory requirements in your request.
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