Modified Oligos are specialized DNA or RNA molecules that have been chemically modified to enhance their stability, specificity, or functionality for various research and applications. These modifications can include the introduction of fluorophores, linkers, quenchers, or specific functional groups, depending on the desired purpose.
Our Modified Oligos Service offers a comprehensive range of modifications to meet the specific requirements of researchers and scientists. With our expertise in synthesis technologies and rigorous quality control measures, we ensure the production of high-quality modified oligos that deliver reliable and reproducible results.
Services Offered
It's important to note that modified oligos may require specialized expertise in both sequence design and chemical synthesis techniques. The choice of modification depends on the specific application, and considerations for stability, specificity, and in vivo compatibility should be taken into account.Below is a table outlining the application areas and requirements for services providing modified oligos:
| Application Area |
Description |
Requirements |
| RNAi (RNA Interference) |
Synthesis of chemically modified siRNA for enhanced stability and efficacy. |
Design of siRNA sequences, expertise in chemically modified nucleotides, purification methods, sequence verification. |
| Antisense Oligonucleotides (ASOs) |
Design and synthesis of modified oligos for therapeutic purposes, gene regulation, or functional genomics. |
Expertise in chemical modifications (e.g., phosphorothioate, 2'-O-methyl), sequence design, purification methods, quality control. |
| Protein Expression Regulation |
Oligos with modifications for controlling gene expression or influencing translation efficiency. |
Design of modified sequences, incorporation of regulatory elements, purification methods, sequence verification. |
| Functional Genomics |
Synthesis of modified oligos for various functional genomics studies, including aptamers or probes with specific functionalities. |
Expertise in incorporating chemical modifications, design of functional sequences, purification methods, validation assays. |
| In Vivo Applications |
Oligos modified for improved in vivo stability, delivery, or pharmacokinetics. |
Knowledge of in vivo applications, expertise in chemical modifications for stability, purification methods suitable for in vivo use, safety considerations. |
| Fluorescently Labeled Oligos |
Synthesis of oligos with fluorescent labels for imaging applications. |
Design of fluorescently labeled sequences, expertise in labeling techniques, purification methods, validation of labeling efficiency. |
When you engage our Modified Oligos Service, you can expect a streamlined and efficient process designed to meet your requirements:
- Consultation: Our experts will consult with you to understand the intricacies of your project. We will take the time to listen to your needs, goals, and challenges. Based on this consultation, we will recommend suitable modifications for your oligos.
- Design and Customization: Once we have a clear understanding of your project requirements, we will proceed with the design and customization of the modified oligos. Our team of experts will leverage their knowledge and expertise to create oligos that align perfectly with your specifications.
- Synthesis and Purification: We employ advanced synthesis techniques and purification methods to ensure the production of high-quality modified oligos. Our commitment to excellence means that we pay meticulous attention to every step of the synthesis process, resulting in reliable and reproducible oligos.
- Quality Control: As part of our stringent quality control procedures, all synthesized oligos undergo thorough analysis and verification of purity, yield, and integrity. We leave no stone unturned in ensuring that the modified oligos meet the highest quality standards.
- Delivery: Once the modified oligos have successfully passed our quality control measures, we will carefully package them to ensure their safety during transit. You can trust us to promptly deliver the oligos to your specified location, providing you with convenience and reliability.
If you have further questions or would like to discuss your specific requirements, please don't hesitate to reach out to us. Our team is dedicated to providing exceptional customer service and assisting you in utilizing modified oligos effectively in your research or applications.
Case Studies
Genome editing has now been reported in many systems using TALEN and CRISPR-Cas9 nucleases. Precise mutations can be introduced during homologydirected repair with donor DNA carrying the wanted sequence edit, but efficiency is usually lower than for gene knockout and optimal strategies have not been extensively investigated. Here, we show that using phosphorothioate-modified oligonucleotides strongly enhances genome editing efficiency of singlestranded oligonucleotide donors in cultured cells. In addition, it provides better design flexibility, allowing insertions more than 100 bp long. Despite previous reports of phosphorothioate-modified oligonucleotide toxicity, clones of edited cells are readily isolated and targeted sequence insertions are achieved in rats and mice with very high frequency, allowing for homozygous loxP site insertion at the mouse ROSA locus in particular. Finally, when detected, imprecise knockin events exhibit indels that are asymmetrically positioned, consistent with genome editing taking place by two steps of single-strand annealing.
(A) Integration activity of short ss- and dsODN donors. TALEN target sequences (in bold) and PAM sequence (in lower cases) in an intron of the PPP1R12C gene within the chromosome 19 locus are shown. Single-stranded donor oligonucleotides (ssODNs) with short homology arms, ss1s (43-mer) and ss2s and ss3s (58-mer), and the 58-bp DS3 duplex (formed by hybridization of ss3s with its complementary strand) were used to make a sequence insertion including a PvuII site at the cleavage site. A control ssODN including a PvuII site but lacking homology arms, GFPss2s-PS, was also used. Doublestranded donors (dsODNs) (different versions of DS1 and DS2, as indicated) included an XhoI site (see sequences in Tables S1 and S2 and Figure S1). dsODNs containing microhomologous ends (DS1-mhDS-PS, DS1-50 mh-PS, DS2-50 mh-PS, DS2-50 mh-PO, and DS1- 30 mh-PS) or not (DS1-blunt-PS, DS1-bluntP-PS, and DS2-50 scr-PS) were evaluated. RFLP analysis of DNA from U2OS cells treated with TALEN AAVS1 or (sgT2+Cas9) and various ssODNs (at 12 mg, except ss2s-PS at 6, 9, and 12 mg) or dsODNs (at 12 mg) is shown. The corresponding rate of PvuII or XhoI cleavage (% RFLP) and of mutations evaluated in parallel by the T7 endonuclease I assay, T7E1 (indicated as % indels; gel not shown) are reported below the gel. PO, phosphodiester; PS, phosphorothioate. Fifty-base-pair DNA ladder (NEB) was shown. See also Figure S1 for integration activity of dsODNs.
(B) ssODNs, but not dsODNs, direct precise sequence insertions. The frequency of the different types of indels, evaluated by deep sequencing, are reported: % indels w/o KI (gray) and KI events that include the precise KI events (black) and KI with additional indels (hatched).
(C) Influence of location and nature of the modification in the oligonucleotide on genome editing efficiency. Different parameters were evaluated: the type of chemical modification (LNA [locked nucleic acid]), the number of modified nucleotides (two at both ends or at 30 end in ss2sPS or ss2sPS_30 , resp.; three at both ends or at the 30 end in ss2s-3PS or ss2s-3PS_30 and ss2s-3LNA_30 , resp.). RFLP rate is shown for different modified oligonucleotides, as mean ± SD (3–20 independent experiments). For all the modified ssODNs compared to the PO ODN, p values from Mann-Whitney statistical analysis are <0.05.
Optimization of Short ODN Donor Design(JB Renaud, et al.,2016)
FAQs
We understand that you may have questions about our Modified Oligos Service. Here are some frequently asked questions and their answers:
Q: What is the turnaround time for Modified Oligos Service?
A: The turnaround time for our Modified Oligos Service may vary depending on the complexity and scale of your project. During the consultation phase, our team will provide you with an estimated timeframe, taking into consideration your specific requirements.
Q: Can you provide modifications not listed in your service highlights?
A: Absolutely! We have the capability to provide custom modifications tailored to your unique needs. Our experienced scientists are well-versed in various modification techniques and can work with you to meet your specific requirements. Please consult with our experts to discuss your modification needs in detail.
Q: What are the recommended storage conditions for modified oligos?
A: To ensure the stability and integrity of modified oligos, we recommend storing them at -20°C or below. This will help maintain their quality and extend their shelf life. Detailed storage instructions will be provided with the delivery of the oligos, giving you peace of mind.
Q: Do you offer bulk discounts for large-scale projects?
A: Yes, we understand the importance of cost-effectiveness for large-scale projects. We offer competitive pricing and attractive bulk discounts for such projects. Please reach out to our sales team with your project details, and they will be happy to discuss pricing options and provide you with a customized quote.
Q: Can you provide technical support for troubleshooting and optimization of modified oligos?
A: Yes, we offer technical support for troubleshooting and optimization of modified oligos. Our team of experts can assist you in addressing any issues or challenges you may encounter during the implementation of modified oligos in your research or applications. Feel free to reach out to us for technical guidance and support.
Q: What is the minimum order quantity for modified oligos?
A: The minimum order quantity for modified oligos may vary depending on the specific modifications and synthesis scale required. Our team will work closely with you to determine the appropriate quantity based on your project needs. Please contact us to discuss your specific requirements.
Q: Do you provide documentation and certificates of analysis with the modified oligos?
A: Yes, we provide comprehensive documentation and certificates of analysis with each batch of modified oligos. These documents include detailed information about the synthesis process, quality control measures, and analytical data. You can rely on these documents for traceability and quality assurance.
Q: Can you assist with the design and optimization of oligonucleotide primers?
A: Absolutely! Our team has expertise in the design and optimization of oligonucleotide primers. Whether you need assistance in primer design for PCR, qPCR, or other applications, we can provide guidance to ensure optimal primer performance. Contact us to discuss your primer design requirements.
Q: Are there any restrictions on the delivery of modified oligos to certain countries?
A: Delivery restrictions may vary depending on the specific modifications and regulations of each country. We are committed to complying with international shipping regulations and will work with you to ensure a smooth and compliant delivery process. Please notify us of any specific delivery requirements or restrictions when discussing your project.
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(X Shen, et al.,2018)
