Bioactive VEGF-C from E. coli

Our article Bioactive VEGF-C from E. coli has been published in Scientific Reports.

You can access the article here: https://doi.org/10.1038/s41598-022-22960-0. As a matter of fact, I did the first experiments expressing VEGF-C in E. coli in 1999, but never got active protein. In the following 15+ years, we exclusively used eukaryotic cells (yeast, S2/Sf9/Hi5 insect cells, CHO) to produce VEGF-C. We reactivated the "VEGF-C in E. coli" project a few years back and we finally reached our goal last year. However, it was much more work than we originally anticipated. In the beginning, all attempts went South, and to rescue the project, we developed an in-vitro folding protocol. It was perhaps more luck than ability that we stumbled upon a combination of solubility tag and redox-modified E. coli strain that can pull off the trick to produce directly bioactive VEGF-C without the need for an in-vitro folding step. We decided to include also our unsuccessful attempts (CyDisCo and periplasmic expression) in the results section to avoid the file drawer effect. The manuscript has been available online as a pre-print since the end of June (https://www.researchsquare.com/article/rs-1776636/v1). In the long long, if we ever are going to use VEGF-C as a protein biopharmaceutical, e.g. in the treatment of lymphedema or ischemic diseases, the ability of produce cheaply large amounts will become important. The clinical studies with VEGF-C to treat lymphedema have been done with a VEGF-C-producing adenovirus (Lymfactin). However, the clinical studies with Lymfactin have been halted after phase II (inconclusive results). Very old data had shown the effect of VEGF-C (delivered as a naked expression plasmid) in ischemia models (Witzenbichler et al. 1999). No serious human studies did follow-up on these early preclinical animal studies, but some - very controversial - experiments have been published a few years back that appear to show a strongly beneficial effect of a single VEGF-C injection in the treatment of myocardial infarction (Klotz et al. 2015).