mRNA Display-based Cell-penetrating Peptides Screening

Cell-penetrating peptide (CPP) has the ability to enter cells together with the attachment, which makes it attractive as a delivery carrier or a direct therapeutic agent. Although about 2000 CPP sequences have been identified, the field is still committed to finding new and more effective CPP for the treatment of incurable diseases. CD BioSciences has accumulated rich experience in peptide research. Using its peptide discovery platform based on mRNA display technology, it can screen new and effective cell-penetrating peptides for drug delivery and therapeutic research.

Introduction into Cell-penetrating Peptides

Cell membrane is the main limiting barrier of intracellular targeted therapy. Overcoming this obstacle can provide new therapeutic possibilities for various human diseases that have not yet been solved. Cell penetrating peptides (CPPs) are usually 4-40 amino acid (AA) long peptides, which can enter cells and enhance the uptake of various molecular goods by cells. They are considered non-toxic and will not permanently damage the cell membrane when entering. In addition, the incorporation or conjugation of CPPs into polymers through physical or chemical modification can produce multifunctional carriers, which can improve the transfection efficiency, prolong the blood circulation time, and enhance the tumor site accumulation and targeting. Although there are several efficient CPPs, they cannot cover a wide range of possible applications. Finding new and efficient CPPs in research, treatment and diagnostic applications remains a challenge.

Fig. 1 Discovery of membrane-permeating peptides via mRNA display. (Bowen, et al., 2020)

mRNA Display for Screening Cell-penetrating Peptides

Over the years, several methods have been developed to search for new CPPs, among which mRNA display is a high-throughput screening method that can be used to select functional peptides and evolve their properties. mRNA display is carried out entirely in vitro. It can scan large libraries of peptide variants, which are several orders of magnitude larger than those that can be screened by other display technologies. In translation, since purinomycin is inserted into the 3' end of the mRNA sequence, the translated peptides remain associated with their mRNA progenitor cells. These mRNA representing peptides can then be used for cell experiments, and only peptide nucleotide conjugates that have been transferred to cells can be enriched and amplified from lysed cells. At present, two peptides with the ability to penetrate cell membrane have been found by mRNA display.

Our Services

Based on mRNA display technology, CD BioSciences can provide global customers with screening and development services of cell-penetrating peptides to support global customers in basic research and drug discovery. Our cell-penetrating peptide screening service process:

1. Design random DNA libraries with fixed length and amino acid sequences of corresponding positions;
2. Construct mRNA display peptide library, transcribe and translate in cell-free system to construct mRNA-peptide complex;
3. For display screening of target cells, repeat the display cycle and amplify the DNA sequence by PCR;
4. Permeability assessment of target cells using cell imaging analysis.

Service Features

CD BioSciences has many years of project development experience in peptide discovery. Based on the mRNA display technology platform, it can provide customers with screening services for various peptides. If you are interested in our services, please contact us for more details.

Reference

1. Bowen, J. D., Schloop, A. E., Reeves, G. T., et al. (2020). Discovery of membrane-permeating cyclic peptides via mRNA display. Bioconjugate Chemistry, 31(10), 2325–2338.

Related Services

• mRNA Display-based High Affinity Peptide Screening
• mRNA Display-based Highly Stable Peptide Screening