Drug Stability Service
Nucleic acid drugs face the challenge of stability in their application. SiRNA is easily degraded by ribozymes in serum when exposed to blood, resulting in a very short half-life in serum. SiRNA is composed of positive and antisense double strand, which is easy to be unspun in vivo. Due to its rich phosphate diester group, siRNA is surrounded by negative charge, so it is difficult for siRNA to pass through the cell membrane. The strong hydrophilicity caused by charge density makes siRNA difficult to interact with albumin and other endogenous proteins in serum, resulting in rapid immune degradation. Natural nucleic acids have only a limited tissue distribution. SiRNA has off-target effect. In the research and development of nucleic acid drugs, the modification of nucleic acid must be broken through in order to improve the stability of nucleic acid drugs and enable them to be successfully applied. Creative Biolabs provides modified design and synthesis services to enhance the stability of nucleic acid drugs.
Creative Biolabs provides solutions for optimization of nucleic acid drugs, including modification of stability and synthesis of nucleic acid drugs service. Creative Biolabs has an advanced and comprehensive laboratory platform and experienced laboratory staff to help customers accelerate the process of nucleic acid drug discovery.
We provide but are not limited to:
- Sugar ring modification. Sugar ring modification is a widely used method of siRNA modification. Type A double helix is essential for siRNA activity, and the role of 2'-OH is not required. Creative Biolabs can assist customers with 2'-O-ME modification, which has good compatibility and can enhance RNA affinity and ribozyme stability.
- The 2'-O-ME modification works best when blunt-ended duplexes are included.
- A variety of properties including strong affinity, ribozyme stability and interfering activity can be optimized by introducing 2'-O-DNP modification into 70% 2'-OH of siRNA double stranded.
- 2'F-RNA is one of the best modified structures. Partial 2'F-RNA modifications can be contained by both positive and anti-sense strands of siRNA, while some siRNA modifications that are all 2'F-RNA modifications are also active. The 2'F-RNA modification significantly increase the serum stability of siRNA and improve the double stranded affinity.
- Phosphor ester chain modification. Some modifications to phosphodiester chains are compatible with RNA interference mechanisms. The ribozyme stability of siRNA modified by borane phosphate is better than that of natural siRNA.
- Double chain structure modification. Small intermally segmented interfering RNA consists of three strands, including a complete antisense strand and two 9-13 nt sense sequences. Compared with traditional siRNA, small intermally segmented interfering RNA has better silencing activity and lower off-target effect.
The popular star product:
- In vivo siRNA/chemical modification siRNA. In vivo siRNA/chemical modification siRNA of Creative Biolabs adopts special chemical modification and can be directly injected into animals. It adopts the international leading synthesis platform, patented process and quality control system, which has the advantages of high efficiency, specificity, stability and low toxicity. In vivo siRNA/chemical modification siRNA can ensure better completion of in vivo experiments.
- Stable chemical modification which can effectively protect siRNA from nuclease degradation.
- Accurate sequence design which can effectively reduce the off-target effect.
- Unique chemical modification which reduce the immune response effectively.
- High efficiency chemical modification to improve bioavailability.
Creative Biolabs adopts unique siRNA chemical modification technology and use high quality raw materials. Through strict quality control system, Creative Biolabs can effectively enhance the in vivo stability of siRNA. The modification does not affect the role of siRNA. This popular star product can reduce immunogenicity and the toxicity of siRNA, meeting the requirement of dosing. Each batch of products can be traced to the source and complete quality documents are provided.
References
- Choung S, et al. Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochemical & Biophysical Research Communications, 2006, 342(3):919-927.
- E. Wang R, et al. Improving the Stability of Aptamers by Chemical Modification. CMC, 2011.
*For Research Use Only. Not for use in diagnostic procedures.