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Engineering Next-Generation Nucleic Acids

Modify the backbone, engineer the sugar, redesign the molecular framework, or expand the genetic alphabet through Bio-Synthesis' integrated Advanced Oligonucleotide Chemistry Platform.

Founded 1984 ISO 9001:2015 ISO 13485:2016 ISO 14001 Custom Chemistry Development Discovery to Scale-Up
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Overview Roadmap Four Platforms Selection Guide Program Workflow Benefits Applications Why Bio-Synthesis FAQ Contact
Overview

Four Dimensions of Nucleic Acid Engineering

Natural DNA and RNA are starting points—not design limits. Advanced oligonucleotide chemistry can modify different structural components of a nucleic acid to tune hybridization, stability, specificity, charge, enzymatic recognition, molecular architecture and genetic information content.

Bio-Synthesis organizes these technologies into four complementary platforms according to the part of the molecule being engineered. This structure helps researchers move from a desired property or application to a practical chemistry strategy without treating each modification as an isolated product.

Advanced Chemistry Platform

Modify, engineer and expand nucleic acid function

Our capability combines advanced synthesis strategy, specialized phosphoramidites and monomers, custom incorporation patterns, purification, analytical characterization and scale-up support across backbone linkage reengineering, sugar-modified XNAs, backbone analog XNAs and artificial base-pair systems.

Discuss Your Chemistry View All Platforms
Backbone Linkage Reengineering

Redesign phosphodiester linkages to control charge, stereochemistry, stability and nuclease resistance.

Sugar Engineering

Tune conformation, affinity, specificity and flexibility.

Expanded XNA Design

Access alternative frameworks and non-natural molecular architectures.

Integrated Program Support

Feasibility, synthesis, purification, QC and scale-up planning.

P

Phosphodiester Linkage

Reengineer internucleotide linkages, charge and stereochemistry.

S

Sugar

Tune conformation, affinity, flexibility and nuclease resistance.

XNA

Framework

Replace the natural sugar-phosphate scaffold with alternative architectures.

B+

Bases

Expand recognition beyond the natural A, T/U, G and C alphabet.

Advanced Chemistry Roadmap

Explore the Complete Platform

Explore Bio-Synthesis’ complete Advanced Chemistry portfolio, organized by the part of the nucleic acid molecule being engineered. Use this roadmap as the visual index to the four platform families below.

Roadmap first. Platform details next.

Select a roadmap lane below or continue to the detailed comparison of purpose, representative chemistries and applications across all four platforms.

Compare the Four Platforms ↓

Backbone Linkage Reengineering

Phosphorothioate & Chiral PS
Methylphosphonate
PACE / Phosphonoacetate
Phosphoramidate
PNA
Morpholino / PMO

View Backbone Linkage details ↓

Sugar-Modified XNAs

LNA & BNA
ENA
Constrained Ethyl (cEt)
2′-O-NMA
2′-AmNA
UNA

View Sugar-Modified XNA details ↓

Backbone Analog XNAs

GNA
TNA
HNA
CeNA
FANA / tcDNA
aTNA / SNA

View Backbone Analog XNA details ↓

Artificial Base Pairs

dP:dZ
dB:dS
dIsoC:dIsoG
dDs:dPx
dNaM:dTPT3
Other custom systems

View Artificial Base Pair details ↓

ROADMAP DRILL-DOWN
Advanced Oligonucleotide Chemistry Platforms

Explore Each Platform in More Detail

The roadmap above provides the portfolio view. The four summaries below explain what each platform changes, which chemistries it includes and when it may be useful.

P–X

Backbone Linkage Reengineering

Reengineer phosphodiester linkages, charge and stereochemistry

Backbone linkage reengineering modifies the phosphodiester connection between nucleotides to improve nuclease resistance, control charge and introduce stereochemical definition. The same platform also includes complete backbone analog technologies such as PNA and Morpholino for steric-blocking and therapeutic designs.

Phosphorothioate Chiral Rp/Sp PS Methylphosphonate PACE Phosphoramidate PNA Morpholino

Explore Backbone Linkage Reengineering

2′

Advanced Sugar-Modified XNAs

Engineer sugar conformation, affinity and flexibility

Sugar-modified XNAs alter or constrain the ribose region to tune duplex stability, mismatch discrimination, biological stability and local flexibility for antisense, hybridization and molecular diagnostic applications.

LNA BNA ENA cEt 2′-O-NMA 2′-AmNA UNA

Explore Advanced Sugar-Modified XNAs

XNA

Advanced Backbone Analog XNAs

Replace the natural sugar-phosphate framework

Backbone analog XNAs use alternative repeating frameworks while retaining programmable base pairing. They open new design space for synthetic genetics, aptamer selection, molecular recognition and nucleic acid nanotechnology.

GNA TNA HNA CeNA FANA tcDNA aTNA SNA

Explore Advanced Backbone Analog XNAs

A+

Artificial Base Pair Systems

Expand the genetic alphabet and molecular recognition

Artificial base pairs introduce non-natural nucleobases capable of selective pairing beyond the four natural bases, supporting expanded information storage, synthetic biology, aptamer discovery and orthogonal molecular recognition.

dP:dZ dB:dS dIsoC:dIsoG dDs:dPx dNaM:dTPT3 AEGIS

Explore Artificial Base Pair Systems

Application-First Selection

Choose Your Engineering Target

Start with the property you want to control. The selector below connects common project goals with the chemistry platform most likely to deserve initial evaluation.

Backbone Linkage Reengineering

Consider backbone linkage reengineering when the primary goal is improved nuclease resistance, altered charge, stereochemical control or steric-blocking performance.

Phosphorothioate Chiral PS PACE Methylphosphonate PMO PNA

Common starting applications

Antisense oligonucleotides, steric-blocking designs, splice modulation, in vivo stability studies and pharmacokinetic optimization.

Advanced Sugar-Modified XNAs

Consider sugar engineering when the goal is higher duplex affinity, improved mismatch discrimination, shorter probe designs or controlled local flexibility.

LNA BNA ENA cEt 2′-O-NMA 2′-AmNA UNA

Common starting applications

Gapmers, splice-switching oligos, qPCR probes, SNP detection, FISH probes, aptamers and hybridization assays.

Advanced Backbone Analog XNAs

Consider alternative XNA frameworks when the program requires non-natural polymer behavior, orthogonal recognition or new molecular geometry.

GNA TNA HNA CeNA FANA aTNA SNA

Common starting applications

XNA aptamers, synthetic genetics, molecular evolution, nuclease-resistant recognition systems and nanotechnology.

Artificial Base Pair Systems

Consider expanded base pairs when natural Watson-Crick recognition does not provide enough information capacity, orthogonality or chemical diversity.

dP:dZ dB:dS dIsoC:dIsoG dDs:dPx dNaM:dTPT3

Common starting applications

Expanded genetic alphabets, synthetic biology, aptamer selection, molecular diagnostics, data storage and protein engineering research.

Advanced Chemistry Program Workflow

From Research Objective to Application-Ready Oligonucleotide

The program workflow begins with the desired biological or analytical function—not with a predetermined modification. Chemistry selection, manufacturability and analytical planning are evaluated together.

01
Research Objective Define the biological, diagnostic or synthetic goal.
02
Target & Sequence Review sequence, target region, architecture and assay constraints.
03
Select Platform Backbone linkage, sugar, XNA framework or artificial base pair.
04
Design Pattern Choose positions, density, stereochemistry and compatible combinations.
05
Synthesis & Purification Develop a route appropriate for chemistry, length and scale.
06
Analytical QC Confirm identity, purity, composition and project-specific attributes.
07
Application Advance into therapeutics, diagnostics, synthetic biology or nanotechnology.
Benefits of Advanced Chemistry

Why Engineer Beyond Conventional DNA and RNA?

Natural hybridization behavior Affinity and mismatch discrimination are limited by the native sugar-phosphate framework.
→
Tunable hybridization Constrained sugars and alternative frameworks can increase or deliberately reduce local duplex stability.
Biological instability Unmodified oligonucleotides may be rapidly degraded by nucleases.
→
Engineered resistance Backbone and sugar strategies can improve stability for selected research and therapeutic designs.
Four-base information system Natural nucleic acids rely on A, T/U, G and C.
→
Expanded molecular recognition Artificial base pairs can add orthogonal pairing and greater information capacity.

Performance Control

Tune affinity, mismatch discrimination, nuclease resistance and local structural behavior through deliberate chemistry placement.

Biological Engineering

Adjust charge, protein interactions, uptake, pharmacokinetic behavior and compatibility with therapeutic mechanisms.

New Molecular Functions

Create expanded recognition systems, alternative scaffolds and integrated designs unavailable to conventional DNA or RNA.
Technology Applications

Applications Enabled by Advanced Chemistry

The same chemistry platform can support very different functions depending on sequence, placement, architecture and formulation. The application should guide the chemistry—not the other way around.

Therapeutic Oligonucleotides

Improve stability, affinity, pharmacology and mechanism-specific behavior across therapeutic modalities.

Antisense Gapmers Splice-Switching Oligos RNAi & siRNA

Detection & Diagnostics

Enhance short-probe performance, mismatch discrimination and target recognition in demanding assays.

qPCR Probes SNP & Mutation Detection FISH & Imaging Probes

Discovery & Synthetic Biology

Extend molecular diversity and recognition for selections, genome engineering and non-natural information systems.

Aptamer Engineering CRISPR & Gene Engineering Artificial Genetic Systems

Programmable Molecular Systems

Use alternative scaffolds and orthogonal interactions for advanced assembly, nanotechnology and materials research.

Nucleic Acid Nanotechnology Supramolecular Assembly Custom XNA Architectures
Why Choose Bio-Synthesis

One Partner Across Chemistry, Synthesis and Characterization

Advanced chemistry requires integrated decisions.

Sequence, modification placement, synthesis route, purification and analytical strategy must be considered as one connected program.

Since 1984

Custom biomolecule synthesis experience

4 Platforms

Backbone linkage, sugar, XNA framework and artificial bases

One Team

Design review through analytical release

R&D

Custom Chemistry Development

Feasibility review for specialty phosphoramidites, customer-supplied reagents, linkers and confidential structures.

QC

Integrated Analytical Planning

HPLC, LC-MS, MALDI-TOF, HR-LC-MS and project-specific methods selected according to molecular complexity.

Scale

Discovery Through Scale-Up

Programs can progress from feasibility quantities through larger research, preclinical and manufacturing requirements.

Team

Scientific Design Support

Chemistry selection, modification density, manufacturability, purification and QC are reviewed together before synthesis.

Quality Systems Supporting Advanced Chemistry Programs

Documented workflows, traceable materials, controlled production and fit-for-purpose analytical release support advanced oligonucleotide programs under Bio-Synthesis quality systems.

ISO 9001:2015 Quality management system
ISO 13485:2016 Medical-device quality framework
ISO 14001 Environmental management system
GLP / cGMP-Aligned Options Program-specific documentation and control

FAQ

What is advanced oligonucleotide chemistry?
It refers to chemical strategies that modify or replace structural elements of DNA and RNA to tune affinity, stability, specificity, charge, biological behavior or information content.
How do backbone linkage reengineering and backbone analog XNAs differ?
Backbone linkage reengineering modifies internucleotide linkages or selected backbone properties. Backbone analog XNAs use alternative molecular frameworks that replace substantial portions of the natural sugar-phosphate scaffold.
Can multiple advanced chemistries be combined?
Often yes, when the synthesis route and molecular design are compatible. A feasibility review should consider sequence, placement, modification density, purification and analytical requirements.
Which chemistries are commonly evaluated for higher affinity?
LNA, BNA, ENA, cEt and selected NMA or AmNA designs are common starting points. UNA is different because it adds flexibility and can reduce local duplex stability.
Which chemistries can improve nuclease resistance?
Phosphorothioate and other backbone strategies, constrained sugar analogs and alternative backbone systems can improve resistance, depending on sequence and application.
What are artificial base pair systems?
They introduce non-natural nucleobases that selectively pair beyond A, T/U, G and C, enabling expanded information content and orthogonal recognition.
Can Bio-Synthesis evaluate custom or unpublished structures?
Yes. Bio-Synthesis can review customer structures, specialty phosphoramidites, supplied reagents, custom linkers and confidential development requirements.
What should I provide for a feasibility review?
Provide the sequence, chemistry name or structure, modification positions, requested scale, purification, analytical requirements and intended application.
More FAQsAll FAQs
Before Requesting a Quote

Information Helpful for Advanced Chemistry Programs

Sequence

DNA, RNA, mixed or XNA format

Chemistry

Name, structure or supplier reference

Placement

Terminal, internal or patterned

Application

Therapeutic, diagnostic or research

Scale

Discovery through manufacturing

QC

Purity, identity and custom testing

Contact & Quote Request

Ready to design an advanced oligonucleotide?

Share your sequence, desired property, proposed chemistry, modification pattern, scale, purification and analytical requirements. Bio-Synthesis can help evaluate chemistry selection and manufacturability before synthesis.
Request a Quote Speak to a Scientist

Need help before quoting?

Email: info@biosyn.com
Phone: 800-227-0627 (US/CAN)
Phone: +001-972-420-8505 (INT)

Advanced Chemistry Platforms

Move directly to the detailed platform overview best aligned with your design.

Backbone Linkage Reengineering Sugar-Modified XNAs Backbone Analog XNAs Artificial Base Pairs

Related Applications

Advanced chemistry can support multiple oligonucleotide modalities and analytical platforms.

Therapeutic Oligos RNAi Gapmers qPCR Probes Aptamers

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, write-ups, 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 design of products intended for their experiments before submitting
their designs to Biosynthesis for production feasibility review.
Thank you for your understanding.

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