Wednesday 29 April 2015

Small Interference RNA Knocks down the Expression of Gene CCP22



TGF β-Smad had wide signaling pathways involved in the regulation of various life processes, such as cell growth, differentiation, apoptosis, extracellular matrix formation and development. In these processes, Smad4 played a core role. Research shows tumorigenesis is associated with Smad4.

The domain (CCPmodule) of Complement control protein (CCP) was first discovered in 1987. There are two categories of proteins with CCP domain, regulators of complement activation (RCA) and non-regulators of complement activation (non - RCA). The CCP domain has an important function which can be combined with antigen molecules involved in cell signal recognition.

RNAi Gene Knockdown


CCP22 is a new and not reported gene gained by using yeast two hybrid screening from DNA Library of human breast interacted with Smad4. The full-length of CCP22 gene is 4494bp, encoding a protein of 1497 amino acid residues. With existing data combined bioinformatics analysis, it is found that the protein encoded by this gene contains 21 CCP elements and 2.5 CCP sequence elements. So the gene was named CCP22.

Protein with different CCP domains, its domains are relatively conservative. But there are some differences in the number of them. Research shows that the proteins with CCP domains may also contain a transmembrane domain, receptor binding domain and other domains. Unlike other proteins with CCP domains, CCP22 only has a CCP domain. So in the CCP family of proteins, it is not clear about its ownership. The study on CCP22 contributes to the understanding of Smad4. It is possible to associate tumor development with immune complement, providing new molecular targets for drug therapy. To this end, small Interference RNA Knockdown is constructed. Western blot shows that siRNA can effectively reduce the expression of CCP22 protein.

Conditional Knockout Service Model

At present, there are 3 main ways to get siRNA, chemical synthesis, in vitro transcription and siRNA recombinant expression vector construction. PSilencer2 is choosing as the siRNA expression vector. 1U6neo has RNApolIII promoter, and has the efficient, cheap and convenient advantages. The FlagCCP22 recombinant expression vector and CCP22siRNA recombinant vector are transfected into HEK293T cell line. Western blot shows that CCP22siRNA can effectively reduce the protein expression level of FlagCCP22. At the same time, CCP22siRNA can also reduce the endogenous CCP22 protein expression level, to lay a solid foundation for further study on the function of CCP22 protein.

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Friday 10 April 2015

Principles and Applications of CRISPR/Cas9 System



CRISPR is a kind of immune mechanism from invading viruses DNA or other exogenous DNA. In bacteria and archaebacteria fields, CRISPR system can be divided into 3 classes, class I and class III needs a variety of CRISPR related protein (Cas protein) to play a role, and class only needs Cas protein, which is widely used to provide convenient conditions.

At present, the application of CRISPR-Cas9 system from Streptococcuspyogenes is the most wide one.Cas9 protein contains two nuclease enzyme domains which can cut two DNA single strands.Cas9 first combines with crRNA and tracrRNA, and then goes through PAM sequence to get into DNA, forming RNA-DNA complex structure, so that cut the DNA double stands.
CRISPR /Cas9 Mice Models

Because the PAM sequence has the advantages of simple structure. A large number of targets can be found almost in all genes. So it has been widely used.CRISPR-Cas9 system has been successfully applied to the plant, bacteria, yeast, fish and mammalian cells. It is currently the most efficient genome editing system.

By means of genetic engineering, sgRNA gained by the improvement of crRNA and tracrRNA which are connected together.RNA fused has the same activity with the wild type RNA, but because its structure is so simple so it is more convenient for users. By linking the originals of expressed sgRNA and Cas9,there can obtained plasmids expressing them two at the same time and the plasmids will be able to operate on the target gene.

Constitutive Knockout Model Service

Now the most common method to study the Cas9 is through plasmids. Although common plasmids also can achieve the effect mostly, but plasmid transfection has the disadvantages of low efficiency and short action duration. Virus appearance solves the problems of common plasmids. Common virus are lentivirus and adenovirus. Lentivirus, commonly used addgene (lentiCRISPRv2, lentiGuide-Puro, lentiCas9-Blast).It can be integrated into the host genome, expressing in a long-term stable way. But because of the slow virus clone ability and the large CAS9 molecular weight (more than 4KB), lower titer and the disadvantages that long insertion may lead to chaos, miss, adenovirus has more advantages. Adenovirus has a strong cloning ability. And when taking into use, it effects for a long time compared with normal plasmids, and can achieve more ideal knockout effect in the end.

Contact Creative Animodel
45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: + 1-631-626-9181
Website: http://www.creative-animodel.com