We have been particularly successful in applying our technology to produce viral antigens and other complex proteins. For example, C-PERL recently completed successful nonhuman primate efficacy trials for a subunit vaccine based on four vaccinia protein antigens (NIAID Challenge grant 1UC1-AI-67129-01).  This work continues with the variola homologs in collaboration with the University of Pennsylvania (NIAID U01-AI-77913-01). 

We have been similarly successful in the production of high yields of high quality norovirus virus-like particles (VLP’S) from multiple isolates, suitable for evaluation as vaccine component candidates.  We have also demonstrated our system to be very capable of producing complex and highly processed proteins including a Fab fragment (O’Connell et al., 2007), biologically-active enzymes, human growth factors and bioscavengers including cholinesterases and paraoxonases, among others.  Moreover, our platform is readily scalable with minimal optimization required, enabling C-PERL to deliver unprecedented quantities of difficult proteins and antigens in a short amount of time.

The PERLXpress System.  Successful protein expression in whole insects is not a new concept.  The use of larvae was pioneered with the silkworm, Bombyx mori, for the production of interferon (Maeda et al., 1985) and mouse interleukin-3 (Miyajima et al., 1987), and this host insect continues to be extensively used both for research and industrial protein production (Mann et al., 2002, Nagaya et al., 2004, Muneta et al, 2003).

The Baculovirus Expression Vector System (BEVS) has been widely used for the production of recombinant proteins. Insect cells enable the over expression of heterologous genes driven by strong promoters and provide essential components for the synthesis of properly folded and post-translationally modified complex proteins (O’Reilly 1994). Insects possess the vast majority of post-translational pathways of mammalian cells (see Features & Benefits).  Cultured insect cells have been characterized and exploited with great success for protein expression and the topic of extensive publication and review (Jones 1996, Summers 2006).  However, since some proteins may express more favorably in one tissue type compared with another, whole insects have an inherent advantage over cell lines derived from only a single tissue.  (Click here to see cross-section image)

Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) is the most widely used and accepted baculovirus expression vector.  T. ni is an exceptional host for AcMNPV and has been used extensively for protein production (e.g., Medin 1990, Hale 1999). Specific examples include human receptor kinase domain (Villalba et al., 1989), human adenosine deaminase (Medin et al., 1990), human Group II Phospholipase A2 (Tremblay et al., 1993), interleukin-2 (Pham et al., 1999; Cha et al. 2002), and the cardiac sodium-calcium exchanger (Hale et al., 1999).

Cloning and expression of target proteins using AcMNPV is well-established for insect cell culture. The PERLXpress System extends the capability to protein production in whole insect larvae by taking advantage of a large number of molecular tools that help ensure high expression levels of functional target protein, in combination with our proprietary automated process for mass rearing and oral infection of synchronously developed larval biomass at Kg/hour throughput rates. Recovery of target protein from the whole insect is performed by standard chromatographic methods to high yields and purity with or without purification tags.

Whether you need to demonstrate proof of concept, have an aggressive analytical schedule or are scaling up to development, the PERLXpress system can fulfill all of your protein production needs.

Link to our Reference Room