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Custom Peptide Design Service for RNAi

With low molecular weight, small in size, cheap, and easy to synthesize, the peptide has become one of the most common ligands used for short dsRNA conjugate and delivery for RNA interference (RNAi). Creative Biolabs owns a group of scientists who have a distinguished understanding of peptide guided delivery system for RNAi. We are confident in providing top-quality peptide design service and peptide short dsRNA conjugation service for RNAi.

Functional Peptides for Small Interfering RNA (siRNA) Delivery

A perfect delivery system for RNAi should be qualified with a compact size, low cytotoxicity, low immunogenicity, free of excessive positive charges, high payload, in vivo stability, efficient endosomolysis, ease of production, flexibility in siRNA selection and affordability. Based on this, peptides are popular alternatives because of their diverse functionalities and biocompatibility. Thus, functional peptides are of great excitement and promise to fill in the long-standing gap of RNAi clinical translation.

CPP-mediated siRNA intracellular delivery. Figure 1. CPP-mediated siRNA intracellular delivery. (Tai, 2017)

Cell-penetrating peptides (CPPs) for intracellular delivery of siRNA are a class of short peptides that can penetrate the cell membrane and translocate into the cytoplasm. By chemical conjugation or noncovalent complex formation with siRNA, CPPs can also bring siRNA inside cells. As of now, more than 100 peptides with this cell-penetrating ability have been identified, and they exhibit a great variety of amino acid sequence, length, and polarity.

As aforementioned, most CPPs enter cells through more than one pathway. For example, they can directly penetrate through cell membranes and carry siRNA molecules into the cytosol where RNAi takes place. At the same time, the majority of CPPs enter cells through the endocytic pathway. Taking cationic CPP R9 as an example, R9/siRNA complexes can enter the cytosol directly, but the majority tend to rapidly accumulate inside endosomes. In general, the endosomolytic activity of CPPs is poor, showing the need of other peptide sequences for endosome disruption, such as conformation-changing fusogenic peptides which are activated by lower pH, chemical structure-changing peptides that remove the masking moieties through chemical reactions, proton buffering peptides which escape the endosome through proton sponge effect.

Many dsRNA binding peptides exist in nature. For instance, the first 172 amino acids in human protein kinase R (PKR) is a double-stranded RNA-binding domain (dsRBD). Once mixed with siRNA, RNA binding motif 1 and 2 of dsRBD wrap around the siRNA backbone with high affinity (Kd=50 nM). Therefore, it can be used as an adaptor to link siRNA molecules with other functional peptides. Compared with cationic peptides and polymers, dsRBD does not introduce excessive positive charges, avoiding non-specific binding and aggregation. Compared with covalent linkage, the plug-and-play preparation is much simpler than perform chemical reactions.


Creative Biolabs is dedicated to providing our customers with high-quality custom peptide design services. Our experienced scientists will help you design the most suitable peptide for short dsRNA (such as siRNA, miRNA, ssRNA) loading. We have generated a series of peptide short dsRNA conjugations and achieved good effects in the in vivo experiment.


Peptides have gained popularity for short dsRNA delivery because of their structural and functional diversity. Creative Biolabs has long-term devoted to peptide design for short dsRNA delivery for RNAi. Our scientists provide high-quality peptide short dsRNA conjugation services to assist our customers’ research and project development. For more detailed information, please feel free to contact us or directly send us an inquiry.


  1. Tai, W.; Gao, X. (2017). Functional peptides for siRNA delivery. Adv Drug Deliv Rev. 110:157-68.

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