Chemical Modifications of Nucleic Acid Drug
Creative Biolabs can supply professional customized service about the chemical modifications of nucleic acid drugs and support of your research and technology appliance.
Nucleic acids therapeutics now nearly reach clinical maturity after decades development. Currently, the Food and Drug Administration (FDA) has approved several nucleic acid drugs and several nucleic acid drugs which are produced by biotechnology and pharmaceutical companies have already been into advanced clinical trials.
The usage of synthetic oligonucleotides for clinical applications has proven to be a rapid and rational method for drug discovery. Researchers can get oligonucleotide-based compounds with drug-like properties by placing the chemical modifications in their structure. To achieve these, the chemical structure of the oligonucleotide needs to be optimized through various modifications including sugar, backbone, nucleobase, and 3'- and 5'-terminal and conjugate modifications.
Advantages of our Chemical Modifications of Nucleic acid drug services:
- Rich experience in chemical modifications of nucleic acids.
- Obtained pure nucleic acids with low impurities.
- Provide various nucleic acid products.
- Conduct large-scale synthesis.
- We will conduct purity verification tests to ensure that the synthetic nucleic acid reaches the target purity, otherwise there is no charge.
We provide but are not limited to:
- Chemical modified nucleotide
- Oligonucleotide conjugatives
Categories of Chemical Modifications:
1. Chemical modification of nucleotides
About the chemical modification of nucleotides, it mainly contains sugar, backbone, nucleobase, and 3'- and 5'-terminal modifications. Rational combinations and design of these can improve their druggability and provide drug-like properties.
We can provide various chemical modified products, including phosphorothioate modified nucleic acids, 2'-O-Me or 2'－MOE modified nucleic acids, phosphate modified, amino modifed and cholesterol-modified nucleic acids etc.
2. Covalent conjugation of nucleic acids
Covalent conjugation of specific moieties to nucleic acids can efficiently improve their stability, selectivity and specific delivery and achieve better clinical effects.
GalNAc is a successful and commercial liver-targeted ligand which has high affinity to asialoglycoprotein receptor (ASGPR). Galnac oligonucleotides can largely improve the delivery efficiency of drugs. We can provide series of these kind of products including Galnac-siRNA, Galnac-ASO and Galnac-microRNA.
Figure 1 GalNAc-modified oligonucleotide associate with ASGPR (Chen et al, 2017)
Peptide oligonucleotides can assist the drugs to pass through cell membranes thus to reach efficient cellular delivery. Our products include peptide-siRNA, peptide-DNA, peptide-RNA and RGD-siRNA.
siRNAs conjugated with neutral hydrophilic PEG polymer (PEG-siRNA conjugates) were demonstrated for systemic gene delivery. The PEG-siRNA conjugates can improve their stability and prolong the half-life of nucleic acid drugs. We can use specific nucleic acids to conjugate with various PEG (mPEG，DSPE PEG，Branched PEG, Biotin PEG，FITC PEG，DBCO PEG，Azide PEG etc) and customize relevant products to meet customers' demand.
References
- Yogesh S. Sanghvi. Large-scale Automated Synthesis of Therapeutic Oligonucleotides: A Status Update. Advances in Nucleic Acid Therapeutics, 2019, 68.
- Anastasia Khvorova, Jonathan K Watts. The chemical evolution of oligonucleotide therapies of clinical utility. Nature Biotechnology, 2017, 35: 238-248.
- Changmai Chen, Zhenjun Yang, et al. Chemical modifications of nucleic acid drugs and their delivery systems for gene-based therapy. Med Res Rev, 2018, 38(1): 1-41.
*For Research Use Only. Not for use in diagnostic procedures.
