Tel:
Email:

Gapmer Oligonucleotide Synthesis

As a professional oligonucleotides preparation service provider, we provide high-quality products as well as antisense oligonucleotides preparation services. Based on our successful experience and technology, we are able to provide customized synthesis of gapmer oligonucleotides, such as LNA gapmer oligonucleotides, for different research purposes and applications. And based on our strict quality control system, we can provide first-class solutions and after-sales service for your projects.

How do you submit a request for our gapmer oligonucleotide synthesis services?

  • Submit Your Inquiry: Initiate the process by contacting us via the website inquiry form or direct email to our technical support team. Please provide essential information including your gapmer sequence(s), target gene or transcript, preferred chemical modifications, and desired synthesis scale.
  • Consult with Our Experts: Engage in a detailed consultation with our oligonucleotide specialists to clarify your research objectives, review sequence design strategies, and finalize modification options tailored to enhance gapmer stability and efficacy.
  • Receive Technical Evaluation: Our team conducts an in-depth feasibility analysis encompassing sequence validation, modification compatibility, and purification requirements. We provide expert recommendations to optimize your gapmer for maximum target specificity and nuclease resistance.
  • Review and Approve Proposal: We deliver a comprehensive service proposal outlining the synthesis approach, purification methods, quality control standards, estimated timelines, and cost structure. You may request adjustments to ensure alignment with your experimental needs.
  • Production and Quality Assurance: Upon approval, our synthesis operations initiate production using advanced solid-phase chemistry and rigorous purification protocols. Each batch undergoes stringent quality testing to guarantee consistency and performance before delivery.

What is Gapmer Oligonucleotide and How to Design It?

A gapmer oligonucleotide typically consists of a central "gap" region of DNA nucleotides flanked by chemically modified nucleotides (often 2'-O-methyl or locked nucleic acids [LNA]) at both ends. This architecture is carefully crafted to balance nuclease resistance, target affinity, and RNase H recruitment.

Design Principles of Gapmer Oligonucleotide

The design of gapmer oligonucleotide involves first identifying the intervening or targeting RNA or DNA sequence, and then selecting a suitable position on the target sequence as a gap region according to the characteristics and requirements of the target sequence. Next, on both sides of the gap region, complementary sequences are designed which can be base complementarily paired with the remainder of the target sequence. When designing a gapmer oligonucleotide, care also needs to be taken to avoid designing sections with repetitive sequences or self-binding, as well as the need to consider the stability and specificity of the nucleic acid. Where available, the design can be aided by the use of auxiliary tools and software, such as online oligonucleotide design tools or gene editing design tools. These tools can provide base complementarity assessment, sequence characterization, and other design parameters.

Comprehensive Services for Gapmer Oligonucleotide Synthesis

BOC Sciences delivers high-performance, fully customized gapmer oligonucleotide synthesis solutions for researchers seeking potent, RNase H-mediated gene silencing tools. Our services go beyond generic synthesis—we operate as an extension of your research team, providing deep scientific insight, technical precision, and end-to-end workflow integration.

ASO Gapmer Library Synthesis Service

BOC Sciences offers a specialized ASO (Antisense Oligonucleotide) Gapmer Library Synthesis Service designed to accelerate high-throughput screening and functional genomics studies. This service enables researchers to efficiently generate diverse gapmer libraries targeting multiple gene sequences or transcript variants, facilitating rapid identification of potent antisense candidates.

  • High-Throughput Capability: Efficient parallel synthesis of large libraries, ranging from dozens to thousands of unique gapmer sequences.
  • Custom Design Integration: Collaborative design optimization based on target gene panels, splice variants, or mutation-specific sequences.
  • Consistent Quality Across Library: Uniform purification standards and batch-to-batch reproducibility, ensuring reliable comparative analysis.
  • Flexible Formats: Delivery as individual oligonucleotides, pooled mixtures, or plate-formatted collections suitable for automated screening workflows.

Leveraging our advanced synthesis platform and quality assurance systems, BOC Sciences empowers your antisense research with robust, high-quality ASO gapmer libraries designed to expedite discovery and validation phases.

Precision-Driven Gamper Engineering

At BOC Sciences, gapmer oligonucleotide design is not based on generic antisense guidelines—we apply a precision-engineering strategy that integrates transcript-specific features, nuclease accessibility, and molecular pharmacology to achieve high knockdown potency and biological fidelity.

(1) Rational Design Based on Target RNA Accessibility

We employ advanced bioinformatics tools—including RNAfold, Sfold, and MFE structural mapping—to predict accessible, single-stranded regions within the target transcript. These regions are essential for efficient hybridization and subsequent RNase H recruitment. Critical criteria include:

  • Minimal secondary structure entrapment (loop or bulge regions preferred)
  • Avoidance of GC-rich or highly structured domains
  • Conservation of target sequences across splice variants or orthologs if needed

This design logic significantly increases the probability of functional knockdown across multiple model systems.

(2) Optimized Gap Architecture for RNase H Activation

Our standard gapmer configuration typically follows the structure: (3–5 modified bases) – (8–10 DNA bases) – (3–5 modified bases).

The central DNA "gap" (gapmer core) is engineered to provide the substrate for RNase H cleavage and the flanking regions are stabilized using 2'-O-methyl, 2'-MOE, or LNA to:

  • Enhance affinity via increased Tm
  • Protect against exonuclease digestion
  • Reduce immune stimulation via TLR9 suppression (especially in CpG-rich sequences)

Each gap is designed with careful thermodynamic profiling, including:

  • Melting temperature (Tm) optimization for hybridization stability (typically 55–65°C)
  • GC-content balance to ensure specificity without off-target hybridization
  • Off-target screening using BLAST, Bowtie, or custom transcriptome filters

(3) Structure–Activity–Stability (SAS) Triad Optimization

We do not treat binding, activity, and stability as isolated properties. Instead, our approach balances:

  • Hybridization strength (modified flanks)
  • Catalytic accessibility (unmodified gap)
  • Biostability (phosphorothioate backbone, base protection)

This SAS triad is iteratively modeled during the design stage, allowing us to predict and mitigate issues such as premature degradation, incomplete knockdown, or non-specific interactions.

Full-Spectrum Chemical Modifications and Conjugation

At BOC Sciences, we understand that the performance and stability of gapmer oligonucleotides critically depend on precise chemical modifications tailored to the intended research application. Our synthesis platform supports an extensive array of advanced modifications that enhance nuclease resistance, binding affinity, and cellular uptake, enabling researchers to optimize therapeutic potential and experimental reliability. Key modification capabilities include:

Modification CapabilitiesDescriptionPrice
Backbone ChemistryWe incorporate full or partial phosphorothioate (PS) backbone modifications to dramatically improve nuclease stability without compromising RNase H activity. Our proprietary protocols ensure uniform PS incorporation, minimizing batch variability and off-target effects.Inquiry
Sugar Moiety ModificationsTo reinforce hybridization affinity and metabolic durability, we expertly integrate:
  • Locked Nucleic Acid (LNA) nucleotides at strategic flanking positions for enhanced thermal stability and target specificity.
  • 2'-O-methyl (2'-OMe) and 2'-O-methoxyethyl (2'-MOE) modifications to reduce immune activation and improve pharmacokinetics. Our custom chemistry approach allows flexible placement and ratios of modified sugars to balance potency and safety.
Inquiry
Nucleobase ModificationsWhen required, BOC Sciences can introduce nucleobase analogues to reduce off-target interactions or incorporate fluorophores for tracking and imaging studies.Inquiry
Terminal Functionalizations and LabelsWe offer a broad portfolio of 5' and 3' conjugations, for example:
  • Fluorescent dyes (e.g., FAM, Cy3, Cy5) for visualization in cellular uptake and biodistribution assays.
  • Biotin and digoxigenin tags for affinity purification or detection assays.
  • Amine and thiol groups for downstream conjugation with targeting moieties or carriers.
Inquiry
Targeted Conjugation Services To enhance cellular delivery and tissue targeting, our team custom conjugates gapmers with peptides, lipids, cholesterol, or polyethylene glycol (PEG). These modifications improve pharmacodynamics by facilitating endosomal escape, reducing renal clearance, or enabling receptor-mediated uptake.Inquiry

Each modification is applied using proprietary optimized chemistries and synthesis protocols that preserve oligonucleotide integrity and biological function. Our stringent in-process monitoring guarantees the accuracy and reproducibility of complex modifications, ensuring that your gapmers perform exactly as designed.

Step-by-Step Workflow of Gapmer Oligonucleotide Synthesis

The synthesis of gapmer oligonucleotides at BOC Sciences follows a meticulously controlled, multi-stage workflow designed to ensure precision, reproducibility, and high purity. Each stage is optimized to address the unique chemical complexities and modification patterns of gapmers, delivering products that meet stringent research standards.

01

Sequence Design and Validation

  • Collaborate with clients to finalize target sequences
  • Utilize bioinformatic tools for secondary structure analysis and off-target risk assessment
02

Solid-Phase Oligonucleotide Synthesis

  • Automated phosphoramidite chemistry performed on solid supports
  • Incorporation of chemically modified nucleotides (LNA, 2'-OMe, etc.) according to design
03

Cleavage and Deprotection

  • Release of oligonucleotide from resin
  • Removal of protecting groups under controlled chemical conditions compatible with modifications
04

Purification and Analysis

  • Primary purification using high-resolution HPLC or PAGE methods
  • Optional secondary purification for ultra-high purity requirements
05

Quality Control and Characterization

  • Mass spectrometry (MALDI-TOF/ESI-MS) for molecular weight confirmation
  • UV absorbance for concentration and purity assessment
  • Additional analysis (CE, LC-MS) as needed for impurity profiling
06

Formulation and Packaging

  • Preparation in client-specified buffers or lyophilized form
  • Sterile, aliquoted packaging with complete documentation
07

Final Inspection and Shipping

  • Batch review against quality specifications
  • Packaging optimized for stability and logistics
  • Delivery with detailed Certificate of Analysis

This structured workflow ensures that every gapmer oligonucleotide from BOC Sciences meets stringent quality standards, enabling reliable and reproducible outcomes in your preclinical research.

Key Benefits of Choosing Our Gapmer Oligonucleotide Synthesis

1. Precision Chemical Modification for Enhanced Stability and Activity

Our synthesis platform incorporates state-of-the-art chemical modifications—including phosphorothioate backbones and high-affinity flanking nucleotides such as LNA and 2'-MOE—resulting in gapmers with exceptional nuclease resistance and improved target binding. This precision engineering ensures sustained activity in biological systems, crucial for robust gene silencing.

2. Comprehensive Customization to Fit Your Experimental Needs

We provide flexible design options tailored to your project requirements, including variable oligonucleotide length, modification patterns, and conjugation with functional groups (e.g., fluorescent dyes, biotin, peptides). This adaptability supports diverse applications from functional genomics to molecular diagnostics.

3. Rigorous Quality Control and Batch Consistency

Every gapmer oligonucleotide undergoes multi-level quality assurance processes—HPLC or PAGE purification, mass spectrometry verification, UV quantification, and optional endotoxin testing. Our strict standards guarantee high purity (>90%) and reproducibility, empowering reliable experimental results.

4. Accelerated Turnaround with Scalable Production

We combine automated synthesis technology with optimized workflows to deliver rapid project completion without compromising quality. Production scales range from small discovery batches to multi-gram quantities, supporting both research and early-stage development phases efficiently.

5. Expert Technical Support and Collaborative Design

Our experienced scientific team offers dedicated support in sequence design, modification selection, and troubleshooting. This consultative approach helps optimize oligonucleotide performance and minimizes off-target effects, saving valuable research time and resources.

Diverse Applications of Our Gapmer Oligonucleotide Synthesis

Gapmer oligonucleotides serve as a powerful tool for targeted gene silencing, enabling precise modulation of gene expression in diverse biomedical research areas. Their unique structural features and chemical stability facilitate effective RNase H-mediated cleavage of complementary RNA, making them indispensable in advanced molecular biology and therapeutic development research.

1. Functional Genomics and Gene Silencing

Gapmers are extensively employed in functional genomics to dissect gene roles by selectively knocking down mRNA transcripts. This targeted silencing allows researchers to delineate gene function, signaling pathways, and molecular networks in both in vitro and in vivo model systems. By transiently or stably reducing expression levels of disease-relevant genes, gapmers enable elucidation of gene contributions to cellular phenotypes, growth, differentiation, and apoptosis.

2. Target Validation in Drug Discovery

In the preclinical drug development pipeline, gapmers serve as critical molecular tools for target validation. Their ability to efficiently silence candidate genes helps assess the therapeutic potential of specific molecular targets before committing to costly small molecule or biologic development. This precise gene modulation reduces the risk of off-target effects commonly observed with other modalities, increasing confidence in target-drug associations.

3. Modulation of Non-Coding RNAs

Non-coding RNAs, including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), have emerged as crucial regulators in gene expression and disease. Gapmer oligonucleotides offer a robust strategy to selectively degrade these often nuclear-localized transcripts that are refractory to traditional RNA interference approaches. This has profound implications in cancer biology, neurodegeneration, and epigenetic regulation research.

4. Antiviral and Infectious Disease Research

Gapmers are increasingly applied in antiviral strategies targeting viral RNA genomes or transcripts essential for replication. By directing RNase H cleavage to these viral sequences, gapmers can effectively suppress viral load and disrupt infection cycles. Their enhanced stability and specificity make them suitable for in vitro and ex vivo evaluation of novel antiviral compounds and mechanisms.

5. Neuroscience and Neurodegenerative Disease Models

The blood-brain barrier and complex neural environment present challenges for RNA therapeutics. Gapmers with tailored chemical modifications show improved pharmacokinetics and stability in neural tissues, making them attractive candidates for modulating pathogenic gene expression in neurodegenerative diseases such as Huntington’s disease, amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease. Preclinical models benefit from gapmer-mediated gene knockdown to study disease progression and therapeutic intervention.

6. Epigenetic and Transcriptional Regulation Studies

By selectively knocking down transcripts involved in chromatin remodeling and transcription factor expression, gapmers allow detailed exploration of epigenetic regulation mechanisms. This contributes to understanding how gene expression is modulated dynamically in development, differentiation, and pathological states.

FAQs about Our Gapmer Oligonucleotide Synthesis

FAQs about sgRNA Services

Related Products

Related Services

Online Inquiry
Verification code
Inquiry Basket