This service is dedicated to the custom synthesis of oligonucleotide conjugates including oligonucleotides carrying lipids, amino acids, peptides or carbohydrates. In addition, they may include other modifications such as phosphorothioate linkages, 2’-O-methyl-RNA, 2’-O-MOE-RNA, 2′-F-RNA, Locked nucleic acids (LNA), modified nucleotides. The oligonucleotides will be prepared in 1 micromol scale. In most cases, the preparation of the conjugates will require the preparation of oligonucleotides carrying reactive groups such as; amino or thiol groups, which will be subjected to a post-synthetic modification. Purification and characterization will include reversed-phase HPLC analysis and mass spectrometry (MALDI-TOF).
Modification of oligonucleotides during and post synthesis to meet user requirements:
Customer benefits
The service benefits from the 40-years’ experience of the researchers participating in the service, with hundreds of scientific communications on improving the methodology used for the synthesis of modified oligonucleotides. This includes fatty acid derivatives, amino acids, cell penetrating peptides and carbohydrates not available from other services. In addition, the service can develop customized solutions for molecules not addressed in the bibliography.
Target customer
The primary audience are research groups and companies working on gene therapy and gene inhibition in the early stages of preclinical development.
References
1) “Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity”. Aviñó, A. et al. Biochim. Biophys. Acta (General subjects), 1863, 1610-1630 (2019).
2) “Synthesis of oligonucleotides carrying amino-lipid groups at the 3’-end for RNA interference studies”. Grijalvo, S. et al. J. Org. Chem., 75, 6806-6813 (2010).
3) “Synthesis and evaluation of 3’ oleyl-oligonucleotide conjugates as potential cellular uptake enhancers”. Navarro, N. et al. SYNLETT, in press (2024). doi: 10.1055/s-0042-1751528.
This service is dedicated to the custom synthesis of modified nucleotides such as nucleoside monophosphates or triphosphates as well as special phosphoramidites or functionalized solid supports functionalized with small molecules resistant to ammonia deprotection for the preparation of oligonucleotide conjugates.
Special nucleotides for oligonucleotide synthesis
For those services identified as outstanding, at least 20% of their capacity is open under competitive access. See Annex 1 of ACCESS PROTOCOL (provided by Nanbiosis) for details on % of openness for each service
Customer benefits
The service benefits from the 40-years’ experience of the researchers participating in the service with hundreds of scientific communications on improving the methodology used for the synthesis of modified oligonucleotides. This includes a range of modified nucleotides and terminal modifications not available in other services. In addition, the service can develop customized solutions for molecules not covered in the bibliography.
Target customer
The primary audience are research groups and companies involved in gene therapy, gene silencing and the development of nucleic acid-based diagnostic tools.
References
1) “Oligonucleotides containing 1’-aminomethyl or 1’-mercaptomethyl-2’-deoxy-D-ribofuranoses: Synthesis, purification, characterization and conjugation with fluorophores and lipids”. Martín-Nieves, V. et al. Bioconjugate Chem, 32, 350-366 (2021).
2) “Efficient bioactive oligonucleotide-protein conjugation for cell-targeted cancer therapy”. Aviñó, A. et al. Chemistry Open, 8, 382-387 (2019).
3) “Thioctic acid derivatives as building blocks to incorporate DNA oligonucleotides onto gold nanoparticles”. Pérez-Rentero, S. et al. Molecules, 19, 10495-10523 (2014).
This service is dedicated to the custom synthesis of modified oligonucleotides including phosphorothioate linkages, 2’-O-methyl-RNA, 2’-O-MOE-RNA, 2′-F-RNA, Locked nucleic acids (LNA), modified nucleotides and several others. The oligonucleotides will be prepared on a 1 micromol scale. Purification and characterization will include reversed-phase HPLC analysis and mass spectrometry (MALDI-TOF).
Synthesis of oligonucleotides at various different scales (100 microg to 5 mg) and purification using HPLC and/or desalting.
Customer benefits
The service benefits from the 40-years’ experience of the researchers involved in the service, with hundreds of scientific communications on improving the methodology used for the synthesis of modified oligonucleotides. This expertise includes a range of modified nucleotides and terminal modifications that are not available in other services. In addition, the service can develop customized solutions for molecules not covered in the bibliography.
Target customer
The primary audience are research groups and companies involved in mutagenesis, gene therapy, gene inhibition, the development of nucleic acid-based diagnostic tools, or the study of nucleic acid structure and nucleic acid-protein interaction.
References
1) “Detection of SARS-CoV-2 virus by Triplex Enhanced Nucleic Acid Detection Assay (TENADA)”, Aviñó, A., et al. Int. J. Mol. Sci., 23, 15258 (2022).
2) “Properties of parallel tetramolecular G-quadruplex carrying N-acetylgalactosamine as potential enhancers for oligonucleotide delivery to hepatocytes”. Clua, A. et al. Molecules, 27, 3944, (2022).
3) “Chemical modifications in nucleic acids for therapeutic and diagnostic applications”. Fàbrega, C., Aviñó, A., Eritja, R. The Chemical Record, 22, e202100270 (2022).
This service is responsible for conducting regulatory studies for the pharmaceutical industry and interested companies. The safety and efficacy studies are carried out using small and large animal models for the different organic systems, also including animal models of different pathologies.
Customer benefits
These studies are carried out under strict quality regulations, certified with ISO-9001 and Good Laboratory Practices (GLP), quality standards that allow the production of high-precision results.
Therefore, safety and efficacy studies in animal models can be carried out in compliance with the strict guidelines of regulatory agencies, ensuring the reliability and traceability of all results and tests carried out in their different services.
Target customer
The services offered in this unit may be of interest to different companies and laboratories that work within the pharmaceutical industry. Companies whose objective is to test possible candidates for molecules, drugs or medical devices in animal models of specific pathologies.
References
Characterization and development of pulmonar formulations
3D bio-impression of scaffolding for regenerative medicine
The assisted reproduction unit has a laboratory with extensive equipment with which to carry out the basic assisted reproduction techniques, among which are extraction of gametes (ovum and sperm), extraction of embryos, sperm analysis, vitrification and devitrification of gametes and embryos, in vitro fertilization (IVF) and ICSI. It also has a small animal surgery to perform surgery on small animals, mainly mice, which is the animal species with which we preferably work. To carry out these techniques, the Assisted Reproduction Unit is equipped with two intracytoplasmic micromanipulation equipment with IMSI, Laser and Oosight systems, embryo biopsy systems, and mitotic spindle vision systems. We also have a piezoelectric device to carry out ICSI with oocytes from different animal species. We have recently incorporated a Time Lapse incubator to evaluate embryonic development; we also have flow cabinets with stereomicroscopes and heaters, plates, incubators with different gas systems, freezing and cryopreservation equipment for gametes and embryos, among others.
Customer benefits
Because our laboratory is one of the few that does research in assisted reproduction with animal models and has all this equipment, in addition to a bank of gametes and cryopreserved embryos, human reproduction clinics that wish to carry out tests with culture methods for oocytes or embryos, they can only be done with animal species, so our laboratory is suitable for this. In addition, the studies can also be carried out under regulatory requirements, since the institution that carries them out is certified in Good Laboratory Practices.
In this way, preclinical studies can be carried out in animal models in compliance with the strict guidelines of the regulatory agencies, ensuring the reliability and traceability of all the results and tests carried out in its different services.
Target customer
This unit can provide services to all those companies that want to carry out quality control for Human Reproduction clinics, studies of in vitro fertilization and viability of embryo culture media, Micromanipulation and microinjection techniques of mouse embryos or other animal species, whether that we have piezo electric. Furthermore, as we have a bank of cryopreserved mouse oocytes and embryos, any company that needs to have a large number of these gametes and embryos can benefit from this service.
Additional information
In addition to having micromanipulation and microinjection equipment that allows us to inject sperm into the cytoplasmic cavity of the oocyte (ICSI). One of these microinjectors has a built-in Oosight system implemented which allows us to non-invasively (without adding dyes) precisely observe the location of the mitotic spindle indicative of the correct development and optimal degree of maturation of the oocyte. This facilitates the selection of the most suitable oocyte for the ICSI or IMSI procedure. In addition, Oosight IS indicates the insertion site of the sperm inside the oocyte so as not to damage sensitive cytoplasmic structures.
Customer benefits
Having these micromanipulation and microinjection equipment that incorporates the Oosight system to evaluate the quality and degree of maturation of the oocytes allows us to offer this service to embryologists who wish to train in this technique and acquire the necessary skills to be able to carry out carry out this Technique in the human clinic. Furthermore, the implementation of this oosight imaging system allows them to become familiar with the internal structures of the oocyte and classify it according to its level of development, learning to differentiate which are the most optimal oocytes to later perform ICSI or IMSI. This equipment and the oosight system
It allows the practical training of students of master’s degrees and specialization courses in human or animal assisted reproduction.
Because our laboratory is one of the few that researches assisted reproduction with animal models and has all this equipment, human reproduction clinics that want to perform tests with animal oocytes or embryos can perform their tests.
In our laboratory, since experiments can only be carried out on animal species, our laboratory is suitable for it. In addition, the studies can also be carried out under regulatory requirements, since the institution that performs them is certified in Good Laboratory Practices.
In this way, preclinical studies can be carried out in animal models in compliance with the strict guidelines of the regulatory agencies, ensuring the reliability and traceability of all the results and tests carried out in its different services.
Target customer
This service can provide assistance and service to all those Human Reproduction companies and clinics that want to carry out in vitro fertilization studies using Micromanipulation and microinjection techniques of mouse embryos or other animal species, since we have a piezoelectric system that facilitates this process. without damaging the oocyte. In addition, they can carry out studies that allow visualization of the internal structures and location of the mitotic spindle, which will allow them to select those oocytes that present the best morphology and are fully mature to be fertilized later.
Additional information
In addition to having micromanipulation and microinjection equipment that allows us to inject sperm into the cytoplasmic cavity of the oocyte (ICSI). One of these microinjectors has a built-in laser system, which allows, by means of small shots, to make a small hole in the membrane of the embryo and, after absorption with specific needles for this process, obtain two or three cells of the trophectoderm and subsequently send these cells to specialized laboratories that perform preimplantation genetic diagnosis studies, to analyze possible abnormalities of the embryo before its transfer and implantation.
Customer benefits
Having these micromanipulation and microinjection equipment that incorporates a laser system to perform trophectoderm biopsy allows us to offer this service to embryologists who wish to train in this technique and acquire the necessary skills to be able to carry out this technique in the human clinic. Furthermore, the implementation of this ICSI technique and blastomere biopsy, and the handling and use of micromanipulators and microinjectors allows the practical training of master’s students and specialization courses in human or animal assisted reproduction.
Because our laboratory is one of the few that researches assisted reproduction with animal models and has all this equipment, human reproduction clinics that want to perform tests with animal oocytes or embryos can perform their tests.
In our laboratory, since experiments can only be carried out with animal species, our laboratory is suitable for this. In addition, the studies can also be carried out under regulatory requirements, since the institution that performs them is certified in Good Laboratory Practices.
In this way, preclinical studies can be carried out in animal models in compliance with the strict guidelines of the regulatory agencies, ensuring the reliability and traceability of all the results and tests carried out in its different services.
Target customer
This service can provide assistance to all those Human Reproduction companies and clinics that want to carry out in vitro fertilization studies using Micromanipulation and microinjection techniques of mouse embryos or other animal species, since we have a piezoelectric system that facilitates this process without damaging the oocyte In addition, they can perform a biopsy of the embryo’s blastomeres in order to later perform genetic studies on it.
Additional information