Login / Register Order My Items
Contact Us
800.227.0627
Contact Us Quote Order Login / Register
Steric‑block splice modulation • exon skipping • next‑gen chemistry

Splice‑Switching Oligonucleotides (SSOs)

Advanced CDMO manufacturing for exon skipping, exon inclusion, and splice correction programs— spanning PMO, PNA, 2′‑MOE, 2′‑OMe, LNA, and NMA‑modified SSOs, with stereochemical backbone control and lateral mixed positional configuration engineering. Manufactured at large scale in the U.S. (Texas).

Talk to a Scientist Chemistry Platform Manufacturing & QC
Large‑scale manufacturing Pharma & biotech Next‑gen NMA chemistry PS/PN backbones Stereochemical configuration Purification + LC‑MS confirmation
Talk to a chemist Request a quote
Overview How SSOs Work Chemistry Manufacturing Comparison Technical Brief FAQ Recommended Reading Contact

Overview

SSOs are steric‑block antisense molecules designed to redirect pre‑mRNA splicing without RNase H cleavage. By masking splice sites or regulatory elements, SSOs can drive exon skipping, exon inclusion, or splice correction outcomes. 1

Compared with standard PS‑only steric‑block offerings, we help teams evaluate chemistry depth + positional control early so leads transition to scale‑up with fewer redesign cycles. Our platform is built for programs that need more than standard chemistries—supporting next‑generation sugar and backbone options, stereochemical configuration, and mixed positional deployment to tune affinity, stability, and developability.

CDMO strength: scale + control

Stage‑appropriate execution from early screens through scale‑up readiness, with purification and analytics engineered around your chemistry.

Program levers

Chemistry
Next‑gen
NMA, PN, hybrids
Control
Positional
Lateral mixed patterns
Scale
Program
Large‑scale capable
QC
Orthogonal
Chrom + LC‑MS
Typical SSO use cases
TherapeuticsRare
Exon skipping

Mask motifs to skip a target exon and restore frame or reduce toxic isoforms.

RescueInclusion
Exon inclusion

Block silencers or strengthen signals to increase inclusion of desired exons.

CorrectionMoA
Splice correction

Redirect aberrant splicing driven by splice‑site or regulatory mutations.

ToolsGenomics
Functional studies

Probe isoform biology with controlled chemistry and positional variants.

Modalities supported
Steric‑block SSO formats including PMO and PNA (charge‑neutral) and modified phosphorothioate‑based SSOs (2′‑MOE, 2′‑OMe, LNA, NMA), including chimeric and positional configuration designs.
Related RNA Therapeutics CDMO Platforms
For programs that require transcript knockdown, see our siRNA manufacturing platform. For RNase H-dependent programs, explore antisense oligonucleotides (ASO). For targeted delivery strategies, see receptor-targeted oligonucleotide conjugation, and for delivery/enabling modalities, explore oligo‑peptide conjugation. Cross-platform chemistry experience helps translate splice modulation programs into scalable, analytics-ready manufacturing.

How SSOs Work

SSOs bind pre‑mRNA and physically block spliceosome recognition at selected motifs (splice sites, enhancers, silencers), shifting splicing to produce the intended isoform outcome. 1

1Bind
Target pre‑mRNA

Sequence‑specific binding to splice motifs and regulatory elements.

2Block
Steric hindrance

Prevents factor recruitment and alters splice‑site usage.

3Shift
Splice outcome

Exon skipping/inclusion to change isoform or restore frame.

Splice-switching oligonucleotide (SSO) mechanism showing steric block of spliceosome recognition on pre-mRNA leading to exon skipping or exon inclusion

Schematic representation of how splice-switching oligonucleotides SSOs bind to pre‑mRNA and physically block spliceosome recognition at selected motifs

Mechanism clarity
Steric‑block SSOs are designed to avoid RNase H recruitment. Chemistry and positional configuration are selected to maximize binding, stability, and splice modulation while keeping the mechanism non‑cleaving.

Chemistry Platforms Supported

We support core and next‑generation SSO chemistries, including NMA and stereochemical/positional configuration approaches used to tune affinity, stability, and manufacturability. 2

Engineering layer Examples supported What it enables Manufacturing notes
Sugar modifications 2′‑MOE, 2′‑OMe, LNA, NMA (2′‑O‑[2‑(methylamino)‑2‑oxoethyl]) Affinity tuning, nuclease resistance, steric‑block performance (RNase H‑independent) Positional placement influences solubility and separation; analytics confirms modification completeness
Backbone linkages PS, mixed PO/PS, PN (phosphoryl guanidine), chimeric backbones Improved stability and pharmacology; backbone‑driven performance optimization Method development tuned to chemistry; impurity planning for close‑running species
Stereochemical control Rp/Sp configuration (design‑dependent), stereopure/chimeric patterns Additional lever for potency and consistency in backbone‑driven designs Configured patterns require positional control and clear documentation
Charge‑neutral platforms PMO, PNA Reduced non‑specific protein binding; robust steric‑block formats Backbone‑specific purification and analytics approach (as applicable)
Next‑gen highlight: NMA + mixed positional configuration
Combine NMA sugar engineering with lateral mixed positional configuration and stereochemical backbone patterns to target splice‑critical regions while maintaining scalable synthesis and purification.
Program add‑ons
Chemistry/placement screens • impurity‑resolution method development • analytics bundles

Precision Positional Chemistry Control

Beyond uniform modification patterns, we support lateral mixed positional configuration and stereochemical distribution strategies that deploy chemistry where it matters most—at splice‑critical motifs—while preserving manufacturability. 2

Zoning
Regional modification zoning

Place sugar/backbone changes across functional splice regions.

Patterns
Lateral mixed patterns

Alternate chemistry density to balance affinity and specificity.

Stereo
Stereochemical distribution

Configured Rp/Sp mapping (design‑dependent) for backbone‑driven programs.

Scale
Scale‑aligned designs

Design choices evaluated alongside purification and scalability needs.

What to provide for manufacturing alignment
Target splice outcome (skip/include/correct), sequence(s), chemistry platform(s), positional configuration intent (if any), scale target, purity/QC expectations, and any special constraints (labels, handles, formulation).

Design strategy comparison

A practical way to de‑risk SSO programs is to compare “standard” steric‑block architectures against next‑generation configured designs that add positional and backbone control. Use this table as a quick decision guide.

Dimension Standard steric‑block SSO Next‑gen configured SSO (positional + backbone control)
Chemistry breadth Typically PS backbone + a narrow set of sugars Expanded platform: 2′‑MOE / 2′‑OMe / LNA / NMA, PS/PO mixes, PN options, charge‑neutral PMO/PNA
Placement strategy Uniform modification patterns Lateral mixed positional configuration and zoning across splice‑critical motifs
Backbone configuration Non‑configured stereochemistry Design‑dependent stereochemical configuration or defined backbone patterns where required
Developability focus Potency-first screens; manufacturability evaluated later Potency + manufacturability co‑optimization: impurity profiles, solubility, and purification behavior evaluated early
Scale‑up readiness Often requires redesign after early success Scale-ready checkpoints baked in (batch traceability, analytics bundle, purification strategy)

Manufacturing, Purification & Analytics

SSOs introduce chemistry‑driven CQAs such as backbone integrity, modification completeness, and close‑running impurity profiles. Our workflow is structured to support program progression with scalable execution and documentation.

Scale Ready
Scale‑ready execution

Program‑dependent scale from mg through multi‑gram and beyond, with scale‑up checkpoints and batch traceability.

Purification Resolve
Impurity‑resolution strategy

Methods engineered to separate truncated species and chemistry‑dependent byproducts—especially for close‑running impurity profiles.

Analytics Confirm
Orthogonal confirmation

Chromatography profiles plus LC‑MS confirmation (as applicable), aligned to program stage and chemistry.

Typical deliverables
COA (as applicable), chromatography profiles, LC‑MS confirmation (as applicable), and batch summary aligned to project stage.

Why choose Bio‑Synthesis for SSO CDMO

Next‑generation chemistry depth

Go beyond standard steric‑block offerings with NMA‑modified sugars, PS/PN backbone options, and design‑dependent stereochemical/positional configuration control.

Manufacturing built for scale‑up

Program‑dependent execution from mg through multi‑gram and beyond, with purification strategies engineerelated complex modification profiles and close‑running impurities.

CDMO‑level analytics & documentation

Orthogonal confirmation (chromatography + LC‑MS as applicable), modification completeness verification, and batch traceability aligned to program progression.

Subtle competitive differentiation
Many suppliers focus on uniform backbone recipes. Our approach emphasizes chemistry depth and positional control so you can evaluate splice outcomes and developability early—reducing re‑work when moving from screening to scale‑up.

Talk to a Scientist

Share your splice objective and chemistry intent (including NMA, PN, stereochemical configuration, or positional configuration). We’ll align manufacturing, purification, and analytics to your stage and scale target.

Client‑designed sequences Confidential inputs Large‑scale capable U.S. manufacturing (TX)
What to include in your request
  • Platform (PMO / PNA / 2′‑MOE / 2′‑OMe / LNA / NMA / hybrids)
  • Any backbone patterning (PS/PN, stereochemical configuration)
  • Positional configuration intent (zoning / lateral mixed patterns)
  • Target quantity and QC expectations
Request a Quote Contact

FAQ

What is an SSO and how is it different from an RNase H ASO?

SSOs are steric‑block oligos designed to modulate splicing without recruiting RNase H cleavage, enabling exon skipping/inclusion/correction.

Do you support next‑generation NMA‑modified SSOs?

Yes—NMA (2′‑O‑[2‑(methylamino)‑2‑oxoethyl]) can be incorporated alone or as part of mixed positional configuration designs.

Can you support stereochemical backbone configuration programs?

Yes—where applicable, we can support configured backbone patterns and stereochemical distribution strategies (design‑dependent).

What scales can you manufacture?

Program‑dependent scale from mg through multi‑gram and beyond, with purification and analytical checkpoints designed for scale‑up.

What analytics are typical?

Chromatography profiles plus LC‑MS confirmation (as applicable) and documentation aligned to your program stage.

Can I request chemistry/placement screening sets?

Yes—chemistry panels and positional configuration screening sets can be built to evaluate splice outcome performance and manufacturability.

More FAQ'sAll FAQ's

Technical brief: building scale‑ready SSOs (white‑paper excerpt)

Goal: help teams translate splice modulation biology into manufacturing‑ready oligonucleotide designs. This excerpt highlights the technical levers that most strongly affect splice outcome performance and CDMO developability—especially when programs move from exploratory screens to scale‑up and broader nonclinical packages.
1) Start with mechanism clarity (steric‑block, RNase H‑independent)

SSOs are typically designed as steric blockers: they bind pre‑mRNA and prevent spliceosome recognition of selected motifs. Unlike RNase H ASOs, splice modulation is achieved by blocking access to splice sites, enhancers, or silencers rather than inducing transcript cleavage. The most successful designs therefore prioritize: (i) tight and specific target engagement; (ii) nuclease resistance without RNase H recruitment; and (iii) consistent splice outcome across relevant cell types. Chemistry selection should support that non‑cleaving mechanism.

2) Chemistry is a performance lever—and a manufacturing constraint
The chemistry set you choose defines both biological behavior and how reliably you can manufacture the product at scale. For steric blockers, sugar and backbone choices are used to tune affinity, stability, and tolerability. Common steric‑block chemistries include 2′‑MOE, 2′‑OMe, and LNA, with phosphorothioate (PS) linkages widely used to improve stability. Programs increasingly evaluate next‑generation options (for example NMA‑modified sugars and PN backbone options) to expand the design space and optimize performance. As chemistry complexity increases, impurity landscapes and purification behavior can change materially—so it is advantageous to evaluate manufacturability alongside potency rather than after a lead is chosen.
3) Positional configuration matters more than “how many modifications”
Uniform patterns are convenient, but splice modulation often depends on precise binding at specific motifs. A “lateral mixed positional configuration” approach (chemistry zoning across splice‑critical regions) can improve target engagement where steric blocking is required while maintaining favorable developability characteristics. In practice, teams often test a small matrix of positional patterns: high‑affinity zones near the functional motif, stability‑oriented zones elsewhere, and spacer architectures or neutral segments when needed for deliverability. This kind of structured exploration can reduce cycle time by converging on a manufacturing‑ready profile earlier in development.
4) Think in CQAs: what must remain controlled as you scale?
For SSOs, critical quality attributes typically include identity, sequence integrity, backbone integrity, modification completeness, and impurity profiles (truncations and chemistry‑dependent byproducts). If stereochemical or configured backbone patterns are used (design‑dependent), documentation and analytical confirmation become more important. A CDMO‑ready plan defines which CQAs are measured at each stage, how methods evolve with scale, and what acceptance criteria align to downstream use. This reduces surprises during scale‑up and increases confidence for nonclinical progression.
5) Purification and analytics should be engineered to the chemistry
Close‑running impurities are common in modified oligonucleotides, and the challenge can increase with certain backbone and sugar combinations. A robust strategy pairs purification method development with orthogonal analytics (chromatography profiles plus LC‑MS confirmation where applicable). When teams plan for these constraints early, they can avoid late redesigns and keep manufacturing aligned with program timelines.
Download the full technical brief (PDF)
Use this for internal alignment and vendor evaluation: chemistry platforms, positional configuration strategy, CQA mapping, and scale‑up checkpoints.
Read Technical Brief

Recommended Reading

Recent reviews and examples relevant to splice-switching SSOs, chemistry, and clinical translation.

  1. Aoki Y. Expansion of Splice-Switching Therapy with Antisense Oligonucleotides. Int J Mol Sci. 2025;26(5):2270. doi:10.3390/ijms26052270.
  2. Splice-switching antisense oligonucleotides for pediatric neurological disorders (review). Frontiers in Molecular Neuroscience. 2024; doi:10.3389/fnmol.2024.1412964.
  3. Sang A, Zhuo S, et al. Mechanisms of Action of the US FDA-Approved Antisense Oligonucleotide Drugs. BioDrugs. 2024;38:511–526. doi:10.1007/s40259-024-00665-2.
  4. Roberts TC, Langer R, Wood MJA. Chemistry, structure and function of approved oligonucleotide therapeutics. Nucleic Acids Res. 2023;51(6):2529–2557. doi:10.1093/nar/gkad104.
  5. Wan WB, Seth PP. Targeting RNA with synthetic oligonucleotides: Clinical success invites innovation. Cell Chem Biol. 2023;30(9):1201–1218. doi:10.1016/j.chembiol.2023.07.007.
  6. Molecular Therapy – Nucleic Acids. Article S2162-2531(24)00309-3. 2024. (Splice-switching / nucleic acids focus).
  7. Molecular Therapy – Nucleic Acids. Splice-switching antisense oligonucleotide controlling tumor suppressor REST. Article S2162-2531(24)00137-9. 2024.
  8. bioRxiv. 2025.10.06.680653v1. doi:10.1101/2025.10.06.680653.
Note on next‑gen chemistry
If your program is evaluating NMA or other emerging sugar/backbone chemistries, consider aligning biology screens with manufacturability screens early (impurity profile, solubility, purification behavior) to reduce later redesign cycles.

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.

Quick Links