Custom antisense oligo synthesis

These tools are for ordering antisense oligos (ASOs) between 15-35 nucleotides in length, for oligos outside this range use these links to order custom RNA or custom DNA.

  • Order individual ASOs

    Custom synthesis of 15-35 bases at either 0.05 μmol or 1.0 μmol scale, with the option of HPLC purification.

  • Order multiple ASOs

    Use this online tool to order multiple custom ASOs with the same characteristics (scale, purification and modifications).

Rely on Dharmacon’s 20+ years of oligo synthesis expertise for your ASO needs.

Our tool supports multiple modifications patterns to enhance the stability & binding affinity of the oligo, including phosphorothioate linkages, 2’-O-methyl, locked nucleic acids, and MOE (methoxyethyl) modifications. We also offer flexibility in synthesis scale and purification options to meet your experimental requirements.  Learn more about antisense oligos (ASOs) on our application page.

For more details on Revvity's continued compliance with the United States Framework For Nucleic Acid Synthesis Screening, please see our self-attestation.

We offer a wide selection of chemical modifications that can be applied to both siRNA and single-strand RNA. 

NOTE: Not all modifications are available through online ordering tool. For assistance please contact scientific support

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Showing modifications available for:
  • siRNA
  • ssRNA
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  • ssRNA-Internal
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Standard DNA Bases Short Code
2'-Deoxy Bases (A, C, G, T)
 

2'-Deoxy Bases (A, C, G, T)

Modification Code:
dA, dC, dG, dT

Description:
DNA modification, typically dTdT, has long been the industry standard for modifying siRNA 3'-overhang, while conferring nuclease resistance and preserving siRNA potency. DNA is well-tolerated in the passage strand with little effects on siRNA potency. Only partially DNA substituted guide strands are functional, whereas alternating the DNA modification with 2'-f has created fully substituted, active guide strands.

Unit Structure:

Unit Structure: 2'-Deoxy Bases (A, C, G, T)

Unit Molecular Weight:
dA (313.21)
dC (289.18)
dG (329.21)
dT (304.19)

References:
Elbashir, S. M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. I, 411, 494-498 (2001).
Chiu, Y. L. and Rana, T. M. siRNA function in RNAi: a chemical modification analysis. RNA, 9, 1034-1048 (2003).

 
 A, C, G, T
2'-OMe RNA Bases (A, C, G, U)
 

2'-OMe RNA Bases (A, C, G, U)

Modification Code:
mA, mC, mG, mU

Description:
The naturally occurring 2'-O-methyl (2'-OMe) modification is the first and most extensively tested 2'-substitutions; 2'-OMe slightly enhances the binding affinity toward RNA (Tm increase of 0.5-0.7°C per modification). 2'-OMe modification has been extensively used to generate fully functional siRNAs with higher nuclease resistance, reduced siRNA immunogenicity, and less off-targeting.

Unit Structure:

Unit Structure: 2'-OMe RNA Bases (A, C, G, U)

Unit Molecular Weight:
mA (343.24)
mC (319.21)
mG (359.23)
mU (320.19)

References:
Soutschek, J. et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature, 432, 173-178 (2004).
Allerson, C. R. et al. Fully 2'-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA. J. Med. Chem, 48, 901-904 (2005).

 
 mA,mC,mG,mU
5' Modifications Short Code
5'-Cholesterol
 

5'-Cholesterol

Modification Code:
Chl

Description:
Potential therapeutic oligonucleotides must permeate the cell membrane for optimal activity. The addition of lipophilic groups such as cholesterol to a siRNA enhances gene silencing in vivo. Efficient and selective uptake of cholesterol siRNA conjugates depends on interactions with lipoprotein particles, lipoprotein receptors and transmembrane proteins. High-density lipoprotein (HDL) directs siRNA delivery into liver, gut, kidney and steroidogenic organs, whereas low-density lipoprotein (LDL) targets siRNA primarily to the liver.

Unit Structure:

Unit Structure: 5'-Cholesterol

Unit Molecular Weight:
624.00

References:
Mackellar, C. et al. Synthesis and physical properties of anti-HIV antisense oligonucleotides bearing terminal lipophilic groups. Nucleic Acid Res. 20, 3411-3417 (1992).
Wolfrum, C. et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nature Biotechnology 25, 1149-1157 (2007).

 
 Chl
5'-Fluorescein
 

5'-Fluorescein

Modification Code:
Fl

Description:
Fluorescein is often used in fluorescence experiments to demonstrate the kinetics of folding or substrate binding. Fluorescein is also used as a donor to track optimal changes related to folding or substrate binding to intermolecular interactions. Fluorescein-labeled siRNAs can be used to visualize cellular uptake of siRNA and to quantify siRNA transfection/delivery efficiency.

Unit Structure:

Unit Structure: 5'-Fluorescein

Unit Molecular Weight:
538.47

Extinction Coefficient:
75,000

Excitation/Emission Max:
494 nm/525 nm

 
 Fl
Internal Modifications Short Code
Phosphorothioate
 

Phosphorothioate

Modification Code:
*

Description:
A classic and popular phosphate backbone modification is the phosphorothioate (PS) modification where one of the non-bridging phosphate oxygens is replaced with sulfur. Phosphorothioates have been widely used in antisense and siRNA applications. The majority of therapeutic oligonucleotides contain this modification which is introduced to increase nuclease resistance and facilitate cellular uptake and bioavailability in vivo.

Unit Structure:

Unit Structure: Phosphorothioate

Unit Molecular Weight:
15.97 (additional MW where sulfur replacing oxygen)

References:
Kurreck, J. The role of backbone modifications in oligonucleotide-based strategies, in Therapeutic Oligonucleotides (Kurreck, J. ed.), RSC Publishing, pp 1-22 (2008).
Eckstein, F. Phosphorothioates, essential components of therapeutic oligonucleotides. Nucleic Acid Ther. 24, 274-287 (2014).

 
 *
2'-Fluoro-adenosine
 

2'-Fluoro-adenosine

Modification Code:
2'-F-A

Description:
2'-Fluoro-nucleosides adopt an RNA-type sugar conformation, presumably due to the high electronegativity of fluorine. Fluorine substitution (2'-F) slightly stabilizes dsRNA duplex (~1°C in Tm per modification). 2'-F substitution is among the best tolerated modification types and therefore allows the creation of highly modified, active siRNAs, both strands tolerate 2'-F modifications at most positions and substitution of all siRNA pyrimidines was reported to greatly enhance serum stability and to effective support silencing in vitro and in vivo.

Unit Structure:

Unit Structure: 2'-Fluoro-adenosine

Unit Molecular Weight:
331.20

References:
Chiu, Y. L. and Rana, T. M. siRNA function in RNAi: a chemical modification analysis. RNA, 9, 1034-1048 (2003).

 
 2'-F-A
2'-Fluoro-cytidine
 

2'-Fluoro-cytidine

Modification Code:
2'-F-C

Description:
2'-Fluoro-nucleosides adopt an RNA-type sugar conformation, presumably due to the high electronegativity of fluorine. Fluorine substitution (2'-F) slightly stabilizes dsRNA duplex (~1 °C in Tm per modification). 2'-F substitution is among the best tolerated modification types and therefore allows the creation of highly modified, active siRNAs, both strands tolerate 2'-F modifications at most positions and substitution of all siRNA pyrimidines was reported to greatly enhance serum stability and to effective support silencing in vitro and in vivo.

Unit Structure:

Unit Structure: 2'-Fluoro-cytidine

Unit Molecular Weight:
307.17

References:
Chiu, Y. L. and Rana, T. M. siRNA function in RNAi: a chemical modification analysis. RNA, 9, 1034-1048 (2003).

 
 2'-F-C
2'-Fluoro-guanosine
 

2'-Fluoro-guanosine

Modification Code:
2'-F-G

Description:
2'-Fluoro-nucleosides adopt an RNA-type sugar conformation, presumably due to the high electronegativity of fluorine. Fluorine substitution (2'-F) slightly stabilizes dsRNA duplex (~1 °C in Tm per modification). 2'-F substitution is among the best tolerated modification types and therefore allows the creation of highly modified, active siRNAs, both strands tolerate 2'-F modifications at most positions and substitution of all siRNA pyrimidines was reported to greatly enhance serum stability and to effective support silencing in vitro and in vivo.

Unit Structure:

Unit Structure: 2'-Fluoro-guanosine

Unit Molecular Weight:
347.20

References:
Chiu, Y. L. and Rana, T. M. siRNA function in RNAi: a chemical modification analysis. RNA, 9, 1034-1048 (2003).

 
 2'-F-G
2'-Fluoro-uridine
 

2'-Fluoro-uridine

Modification Code:
2'-F-U

Description:
2'-Fluoro-nucleosides adopt an RNA-type sugar conformation, presumably due to the high electronegativity of fluorine. Fluorine substitution (2'-F) slightly stabilizes dsRNA duplex (~1 °C in Tm per modification). 2'-F substitution is among the best tolerated modification types and therefore allows the creation of highly modified, active siRNAs, both strands tolerate 2'-F modifications at most positions and substitution of all siRNA pyrimidines was reported to greatly enhance serum stability and to effective support silencing in vitro and in vivo.

Unit Structure:

Unit Structure: 2'-Fluoro-uridine

Unit Molecular Weight:
308.16

References:
Chiu, Y. L. and Rana, T. M. siRNA function in RNAi: a chemical modification analysis. RNA, 9, 1034-1048 (2003).

 
 2'-F-U
5-Methyl-Deoxycytidine
 

5-Methyl-deoxycytidine

Modification Code:
5-M-dC

Description:
The nucleobase modification 5-methylcytosine (5-mC) is widespread both in DNA and different cellular RNAs. 5-Methyl-cytosine enhances DNA or RNA duplex stability by elevating melting temperature 0.5 - 1.3°C per addition.

Unit Structure:

Unit Structure: 5-Methyl-Deoxycytidine

Unit Molecular Weight:
303.21

References:

Freier, S. M. and Altmann, K.-H. The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically modified DNA:RNA duplexes. Nucleic Acid Res. 25, 4429-4443 (1997).

 
 5-M-dC
Adenosine Locked Nucleic Acid
 A-LNA
Cytidine (5-methyl-deoxy-cytidine) Locked Nucleic Acid 5mC-LNA
Guanosine Locked Nucleic Acid
 G-LNA
Thymidine Locked Nucleic Acid
 T-LNA
2′-O-Methoxy-ethyl-Adenosine
 moeA
2’-O-Methoxy-ethyl-5-Methyl-Cytidine
 moe5MeC
2′-O-Methoxy-ethyl-Guanosine
 moeG
2’-O-Methoxy-ethyl-Thymidine moeT
3' Modifications Short Code
3'-Cholesterol
 

3'-Cholesterol

Modification Code:
3'-Chl

Description:
Potential therapeutic oligonucleotides must permeate the cell membrane for optimal activity. The addition of lipophilic groups such as cholesterol to a siRNA enhances gene silencing in vivo. Efficient and selective uptake of cholesterol siRNA conjugates depends on interactions with lipoprotein particles, lipoprotein receptors and transmembrane proteins. High-density lipoprotein (HDL) directs siRNA delivery into liver, gut, kidney and steroidogenic organs, whereas low-density lipoprotein (LDL) targets siRNA primarily to the liver.

Unit Structure:

Unit Structure: 3'-Cholesterol

Unit Molecular Weight:
705.94

References:
Mackellar, C. et al. Synthesis and physical properties of anti-HIV antisense oligonucleotides bearing terminal lipophilic groups. Nucleic Acid Res. 20, 3411-3417 (1992).
Wolfrum, C. et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nature Biotechnology 25, 1149-1157 (2007).

 
 3'-Chl
N-acetyl-galactosamine
 GalNAc
3’TEG-Cholesterol
 TEG-Chl-3’