Custom RNA Modifications Service

Custom RNA Modifications involve the precise chemical alteration of an RNA molecule through the site-specific incorporation of non-standard nucleosides, backbone linkages, or chemical groups. These modifications are critical for overcoming the inherent instability of native RNA, enhancing cell uptake, conferring specific functional properties (e.g., fluorescence or cross-linking), and mimicking natural post-transcriptional events (e.g., N6-methyladenosine, m6A). This service is indispensable for advancing RNA therapeutics, molecular diagnostics, and structural biology studies.

CD Biosynsis offers a dedicated Custom RNA Modifications Service featuring one of the industry's largest catalogs of modification chemistries. We specialize in the high-fidelity synthesis of RNA oligos where modifications are introduced at specific, pre-defined positions (5', 3', or internal) to ensure maximum functional impact. Our expertise covers stability enhancers (e.g., LNA, 2'-F), functional probes (e.g., biotin, fluorophores), and base analogs . Combined with mandatory HPLC purification and Mass Spectrometry (MS) verification, we guarantee the delivery of highly pure, structurally correct modified RNA for your most demanding applications.

Highlights

Unmatched expertise in complex RNA modification chemistry:

• Extensive Modification Catalog: Access to hundreds of modified phosphoramidites, including Locked Nucleic Acids (LNA), 2'-F modifications, and fluorescent probes .
• Site-Specific Control: Guaranteeing the precise incorporation of the modification at the exact desired nucleotide position without off-target effects.
• Dual QC Verification: Every modified oligo is verified by Mass Spectrometry (MS) to confirm the mass shift resulting from the modification, plus HPLC for purity.
• Challenging RNA Synthesis: Specialized techniques for synthesizing sequences prone to secondary structure or those incorporating multiple, closely spaced modifications.

Applications

Modified RNA is pivotal for high-resolution research and therapeutic development:

ASO & siRNA Therapeutics

           

Incorporating PTO backbones, 2'-MOE, or LNA modifications to drastically improve pharmacokinetics and cellular stability for drug delivery.

Structural & Binding Studies

Using base analogs (e.g., 2-aminopurine) or photo-crosslinking moieties (e.g., azide groups) to map RNA-protein interactions.

Epitranscriptomics Research

Synthesis of RNA containing natural modifications (e.g., m6A, pseudouridine) to study reader/eraser/writer protein binding and function.

Molecular Diagnostics (Probes)

Dual-labeled TaqMan-style probes or Molecular Beacons combining high-efficiency fluorophores and quenchers for qPCR and FISH.

Modification Types & Capabilities

Specialized chemical synthesis for a comprehensive range of RNA alterations:

Sugar Modifications (2'-Position)

2'-OMe, 2'-Fluoro (2'-F), 2'-Amino, 2'-MOE (Methoxyethyl), and LNA (Locked Nucleic Acid).

Backbone Modifications (Linkage)

Phosphorothioate (PTO) bonds and Phosphorodiamidate Morpholino Oligos (PMO) for nuclease resistance.

Fluorescent Labels and Quenchers

FAM, Cy3/Cy5, Texas Red, Dye terminators, BHQ series, and Dabcyl for visualization and FRET applications.

Base Analogs (Epigenetic Bases)

N6-methyladenosine (m6A), Pseudouridine ($\Psi$), Inosine (I), 5-Methylcytosine (5-mC) and biotin labeled bases.

Conjugates and Functional Groups

Attachment of Cholesterol, Thiol, Amino, Biotin, and Click Chemistry groups at 5', 3', or internal positions.

Workflow

Precision synthesis and rigorous QC ensure the functional integrity of every modified RNA oligo:

• Modification Design Consultation: We advise on the optimal placement and type of modification based on your structural or functional goals (e.g., 3' PTO for stability).
• Specialized Phosphoramidite Synthesis: Modified bases and sugars are incorporated into the RNA sequence using automated solid-phase synthesis with low cap time to maximize coupling efficiency.
• Gentle Cleavage and Deprotection: Customized chemical protocols are used to cleave the oligo from the resin and remove protecting groups without degrading sensitive modifications.
• High-Resolution Purification: Mandatory HPLC purification ensures the isolation of the full-length, desired product, especially critical for heavily modified sequences.
• Quality Control (QC): Verification by Mass Spectrometry (MS) confirms the exact mass corresponding to the sequence and all modifications. Analytical HPLC confirms final purity.
• Delivery: RNA is delivered as a nuclease-free, lyophilized powder with a detailed Certificate of Analysis (COA), MS report, and HPLC data.

We provide essential assurance for successful research using modified RNA:

• Minimizing Steric Hindrance: Expert synthesis planning to ensure that multiple or large modifications can be physically incorporated without causing synthesis failure.
• High Purity Guarantee: The complex nature of modified RNA synthesis requires superior purification; our HPLC guarantees high purity crucial for preventing false positives in sensitive assays.
• Proprietary RNase Control: Strict adherence to RNase-free laboratory conditions throughout the entire manufacturing process.
• Rapid Turnaround Time: Streamlined production protocols allow for faster delivery of custom modified RNA compared to general chemical synthesis providers.