Recombinant pharmaceuticals from microbial cells: a 2015 update

Diabetes, growth or clotting disorders are among the spectrum of human diseases related to protein absence or malfunction. Since these pathologies cannot be yet regularly treated by gene therapy, the administration of functional proteins produced ex vivo is required. As both protein extraction from natural producers and chemical synthesis undergo inherent constraints that limit regular large-scale production, recombinant DNA technologies have rapidly become a choice for therapeutic protein production. The spectrum of organisms exploited as recombinant cell factories has expanded from the early predominating Escherichia coli to alternative bacteria, yeasts, insect cells and especially mammalian cells, which benefit from metabolic and protein processing pathways similar to those in human cells. Up to date, around 650 protein drugs have been worldwide approved, among which about 400 are obtained by recombinant technologies. Other 1300 recombinant pharmaceuticals are under development, with a clear tendency towards engineered versions with improved performance and new functionalities regarding the conventional, plain protein species. This trend is exemplified by the examination of the contemporary protein-based drugs developed for cancer treatment.

[1]  J. Corchero,et al.  Detoxifying Escherichia coli for endotoxin-free production of recombinant proteins , 2015, Microbial Cell Factories.

[2]  F. Meaney,et al.  [Clinical genetics]. , 1982, Nederlands tijdschrift voor geneeskunde.

[3]  J. Powell.  Lasting power of new clotting proteins. , 2014, Hematology. American Society of Hematology. Education Program.

[4]  Alain Cariou,et al.  Toward theragnostics , 2009, Critical care medicine.

[5]  A. Demain,et al.  Recombinant organisms for production of industrial products , 2010, Bioengineered bugs.

[6]  J. Hirschhorn,et al.  A comprehensive review of genetic association studies , 2002, Genetics in Medicine.

[7]  J. Bryant,et al.  Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation. , 2010, Health technology assessment.

[8]  H. Komatsu.  [Antibody therapy in cancer]. , 2010, Nihon rinsho. Japanese journal of clinical medicine.

[9]  G. Cutting.  Modifier genetics: cystic fibrosis. , 2005, Annual review of genomics and human genetics.

[10]  M. Hecker,et al.  Bacillus subtilis: from soil bacterium to super-secreting cell factory , 2013, Microbial Cell Factories.

[11]  S. Taguchi,et al.  Advances and needs for endotoxin-free production strains , 2015, Applied Microbiology and Biotechnology.

[12]  Weijing Sun,et al.  Ziv-aflibercept in metastatic colorectal cancer , 2013, Biologics : targets & therapy.

[13]  R. Mackie,et al.  Heterologous gene expression in filamentous fungi. , 2012, Advances in applied microbiology.

[14]  Human insulin receives FDA approval. , 1982, FDA drug bulletin.

[15]  Rachel Chen.  Bacterial expression systems for recombinant protein production: E. coli and beyond. , 2012, Biotechnology advances.

[16]  Liying Wang,et al.  Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy , 2014, BioMed research international.

[17]  A. Demain,et al.  Production of recombinant proteins by microbes and higher organisms. , 2009, Biotechnology advances.

[18]  A. Villaverde,et al.  Expanding the recombinant protein quality in Lactococcus lactis , 2014, Microbial Cell Factories.

[19]  Esther Vázquez,et al.  Microbial factories for recombinant pharmaceuticals , 2009 .

[20]  P. Wan,et al.  Advances in recombinant protein expression for use in pharmaceutical research. , 2013, Current opinion in structural biology.

[21]  F. Hagemeister,et al.  Denileukin diftitox: a novel immunotoxin , 2009, Expert opinion on biological therapy.

[22]  Antonio Villaverde,et al.  Unconventional microbial systems for the cost-efficient production of high-quality protein therapeutics. , 2013, Biotechnology advances.

[23]  D. J. Weatherall,et al.  Phenotype—genotype relationships in monogenic disease: lessons from the thalassaemias , 2001, Nature Reviews Genetics.

[24]  R. Reski,et al.  Moss bioreactors producing improved biopharmaceuticals. , 2007, Current opinion in biotechnology.

[25]  Gary Walsh,et al.  Biopharmaceutical benchmarks , 2000, Nature Biotechnology.

[26]  B. Chabner,et al.  Chemotherapy and the war on cancer , 2005, Nature Reviews Cancer.

[27]  S. Kushnir,et al.  Development of an inducible protein expression system based on the protozoan host Leishmania tarentolae. , 2005, Protein expression and purification.

[28]  Tim W. Overton,et al.  Recombinant protein production in bacterial hosts. , 2014, Drug discovery today.

[29]  G. Basile,et al.  Recombinant Protein Expression in Leishmania tarentolae , 2009, Molecular biotechnology.

[30]  E. Redwan,et al.  Cell factories for insulin production , 2014, Microbial Cell Factories.

[31]  W. Duckworth,et al.  Recombinant DNA technology in the treatment of diabetes: insulin analogs. , 2001, Endocrine reviews.

[32]  T. Akuta,et al.  Improving the soluble expression and purification of recombinant human stem cell factor (SCF) in endotoxin-free Escherichia coli by disulfide shuffling with persulfide. , 2016, Protein expression and purification.

[33]  N. Ferrer-Miralles,et al.  Bacterial cell factories for recombinant protein production; expanding the catalogue , 2013, Microbial Cell Factories.

[34]  Ronald A Rader,et al.  (Re)defining biopharmaceutical , 2008, Nature Biotechnology.

[35]  Gary Walsh,et al.  Biopharmaceutical benchmarks 2014 , 2014, Nature Biotechnology.

[36]  R. Reski,et al.  Current achievements in the production of complex biopharmaceuticals with moss bioreactors , 2008, Bioprocess and biosystems engineering.

[37]  J. Ritz,et al.  Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. , 2004, Blood.

[38]  Jianwei Zhu,et al.  Mammalian cell protein expression for biopharmaceutical production. , 2012, Biotechnology advances.

[39]  I. S. Johnson.  Human insulin from recombinant DNA technology. , 1983, Science.

[40]  R. Contreras,et al.  Non-pathogenic trypanosomatid protozoa as a platform for protein research and production. , 2002, Protein expression and purification.

[41]  M. McDermott,et al.  Clinical genetics in 2014: New monogenic diseases span the immunological disease continuum , 2015, Nature Reviews Rheumatology.

[42]  A. Villaverde,et al.  Production of functional inclusion bodies in endotoxin-free Escherichia coli , 2014, Applied Microbiology and Biotechnology.