Accelerate your oligonucleotide synthesis and development with a wide variety of Thermo Fisher Scientific phosphoramidites and tools. Our expert product support team is available to guide your screening, development, manufacturing and beyond, ensuring you have the most efficient and reproducible path to commercialization. Take your oligonucleotide synthesis project from early research to preclinical candidate with a single supplier that understands your needs every step of the way.

Oligonucleotide synthesis

Oligonucleotide therapeutics are a new class of drugs comprised of short strings of synthetic nucleotides. Oligonucleotide synthesis is a chemical pathway sequentially incorporating phosphoramidites to grow specific sequences of modified and unmodified DNA or RNA. The resulting molecules can then be used in a variety of applications including forensic and diagnostic assays (PCR, qPCR, and other platforms), nucleic acid therapeutics (RNAi, antisense, aptamer, CRISPR), and basic research (Figure 1). 

Phosphoramidites as the building blocks of oligonucleotide synthesis

Figure 1. A schematic diagram outlines the phosphoramidite oligonucleotide solid phase synthesis method.

Reagents for oligonucleotide synthesis

Thermo Fisher Scientific offers a range of phosphoramidites and solid supports for oligonucleotide synthesis:

DNA Phosphoramidites

  • TheraPure DNA phosphoramidites, the original brand of amidites designed specifically for therapeutic strategies
  • Continued development focuses on demand for high-sensitivity assays and next-generation therapeutic molecules

RNA Phosphoramidites

  • TheraPure RNA phosphoramidites are the gold standard for development and manufacturing of RNA-based therapeutic oligonucleotides
  • Includes 2’-modified RNA phosphoramidites to help increase stability and improve resistance to nuclease activity in vivo

2’ O-methyl (OMe) RNA Phosphoramidites

  • Traditional staple for oligo therapeutics for many years
  • Support novel technologies such as CRISPR-Cas9 gRNA
  • Key component of oligonucleotides designed for antisense, siRNA, aptamer, or gRNA-based applications
  • Modifications offer:
    • Nuclease resistance
      • Fewer off-target effects
      • Increased hybridization affinities
    • Faster deprotection with modified version including PAC-A and iPrPAC-G

2’ O-methyoxy-ethyl (MOE) RNA Phosphoramidites

  • Advanced generation of antisense oligonucleotides and siRNA designs
  • Key component of antisense-based oligonucleotides
  • Modifications offer:
    • Nuclease resistance
      • Fewer off-target effects
      • Increased hybridization affinities

2’ Fluoro (Fl) RNA Phosphoramidites

  • Modifications support stability and affinity for oligos used in therapeutic strategies
  • Recently upgraded to meet standards of TheraPure products
  • Modifications offer:
    • Nuclease resistance
    • Increased thermal stability of RNA duplexes

Linkers and Spacers

  • 3′, 5′, and internal oligo linkers are modifications used for NHS ester conjugation
  • Spacers increase the distance between functional groups, and provide conformational support

Structural Phosphoramidites

  • Used for molecular diagnostics and research applications
  • Modifications for design of primers, probes, or for structural studies
  • Modifications includes 5m-dC, dU, dI, N6-Me-dA, N4-Ethyl-dC, 8-oxo-dG, and more

Customization for oligonucleotide synthesis

Custom chemistries (e.g., triphosphate, phosphoramidites, and custom organic), customized QC, and packaging options including filling and labeling are available.

Customization options available on sugar, base or 5’ protection modification
  1. Dimethoxy (DMT) substitution with alternate protecting groups
  2. Base = A, C, G, T, or U protection modifications or base modifications
  3. Sugar 2’ position modifications and protection options
  4. Phosphoramidite, succinate, and support attachment and proprietary chemistries

Thermo Scientific TheraPure phosphoramidites

Originally designed specifically to meet the needs of oligonucleotide synthesis and development, TheraPure phosphoramidites are now important for therapeutics, molecular assay, and gene synthesis applications, which benefit from low levels of critical impurities. Our Thermo Scientific TheraPure phosphoramidites are designed for oligonucleotide manufacturers requiring highly defined impurity profiles and strictly controlled processes.

DNA Phosphoramidites

  Click images to enlarge

 dA(Bz) CEPdC(Bz) CEPdG(iBu) CEPdT CEP
Cat. No.27-203027-203227-203427-2036
FormulaC47H52N7O7PC46H52N5O8PC44H54N7O8PC40H49N4O8P

RNA Phosphoramidites

  Click images to enlarge

 Bz-rA CEPiBu-rG CEPAc-rC CEPrU CEP
Cat. No. 27-190327-190627-180527-1804
FormulaC53H66N7O8PSiC50H68N7O9PSiC47H64N5O9PSiC45H61N4O9PSi

2’-MOE RNA Phosphoramidites

  Click images to enlarge

 2′-MOE-A CEP2′-MOE-5mC CEP2′-MOE-G CEP2′-MOE-T CEP
Cat. No.27-101927-102027-102227-1021
FormulaC50H58N7O9PC50H60N5O10PC47H60N7O10PC43H55N4O10P

2’-Fluoro RNA Phosphoramidites

  Click images to enlarge

 2′-Fluoro-Bz-A-CEP2′-Fluoro-iBu-G-CEPTheraPure 2′-Fluoro-Ac-C-CEPTheraPure 2′-Fluoro-U-CEPTP 2'-Fluoro-Ac-G-CEP
Cat. No.27-160127-160727-160427-1602SY5410*
FormulaC47H51FN7O7PC44H53FN7O8PC41H49N5FO8PC39H46FN4O8PC42H49FN7O8P

* For more specification details, contact us.

2’ O-methyl (OMe) RNA Phosphoramidites

  Click images to enlarge

 2′-OMe-Bz-A-CEP2′-OMe-U-CEP2′-OMe-iBu-G-CEP2′-OMe-Ac-C-CEP
TheraPure phosphoramidites' 
Cat. No.		27-204227-204427-204627-2043
FormulaC48H54N7O8PC40H56N7O9PC45H56N7O9PC42H52N5O9P

Enabling oligonucleotide synthesis and development

Manufacturing excellence and expertise

With over 4 decades of engineered nucleic acid manufacturing experience, phosphoramidites combine our expertise in protection chemistries, modifications, manufacturing scale-up, and innovative purification strategies. All catalog (and custom) phosphoramidites are manufactured in our state-of-the-art Milwaukee, WI manufacturing facility, with an ISO 9001:2015 certified quality management system.

Quality manufacturing and regulatory documentation

Processes are monitored from material procurement through final QC and product release, providing batch-to-batch reproducibility. Our rigorously controlled manufacturing processes minimize levels of reactive P(III) impurities which could be incorporated into the oligonucleotide during synthesis and result in the accumulation of by-products. TheraPure phosphoramidites from Thermo Fisher Scientific are designed for pharmaceutical manufacturers looking for core building blocks to use in research and manufacturing. These reagents are crafted in facilities with thoroughly documented quality systems and audited by accredited registrars.

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Related areas

mRNA purification solution   |   Gene therapy research   |   OEM and commercial supply   |   In vitro transcription

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For Research Use Only. Not for use in diagnostic procedures.

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