The trials and tribulations of producing the first genetically engineered drug

Johnson, Irving S.

doi:10.1038/nrd1179

Cited by 19 publications

(9 citation statements)

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“…[53][54][55] The project involved enormous regulatory and even political challenges due to the restrictive environment regarding rDNA, at that time. 4,56 The safety of the approach was hotly debated in public forums, while the ability to produce large quantities at a purity and cost comparable to animal-sourced hormone was scientifically controversial.…”

Section: Biosynthesismentioning

confidence: 99%

Insulin structure and function

2007

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Throughout much of the last century insulin served a central role in the advancement of peptide chemistry, pharmacology, cell signaling and structural biology. These discoveries have provided a steadily improved quantity and quality of life for those afflicted with diabetes. The collective work serves as a foundation for the development of insulin analogs and mimetics capable of providing more tailored therapy. Advancements in patient care have been paced by breakthroughs in core technologies, such as semisynthesis, high performance chromatography, rDNA-biosynthesis and formulation sciences. How the structural and conformational dynamics of this endocrine hormone elicit its biological response remains a vigorous area of study. Numerous insulin analogs have served to coordinate structural biology and biochemical signaling to provide a first level understanding of insulin action. The introduction of broad chemical diversity to the study of insulin has been limited by the inefficiency in total chemical synthesis, and the inherent limitations in rDNA-biosynthesis and semisynthetic approaches. The goals of continued investigation remain the delivery of insulin therapy where glycemic control is more precise and hypoglycemic liability is minimized. Additional objectives for medicinal chemists are the identification of superagonists and insulins more suitable for non-injectable delivery. The historical advancements in the synthesis of insulin analogs by multiple methods is reviewed with the specific structural elements of critical importance being highlighted. The functional refinement of this hormone as directed to improved patient care with insulin analogs of more precise pharmacology is reported.

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Section: Biosynthesismentioning

confidence: 99%

Insulin structure and function

2007

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“…The emergence of biotechnology was a transformational event in the course of the life sciences, yet this was hardly the consensus opinion at its inception. The pioneers of this technology confronted numerous regulatory hurdles related to public and patient safety, in addition to the inherent challenges of producing biosynthetic proteins . With few exceptions, the majority of pharmaceutical companies largely dismissed biotechnology as a source of breakthrough medicines and continued to favor traditional small molecule paradigms.…”

Section: Synthesis As An Enabler Of Biologymentioning

confidence: 99%

Max Bergmann award lecture:Macromolecular medicinal chemistry as applied to metabolic diseases

DiMarchi

Mayer

Gelfanov

et al. 2018

Journal of Peptide Science

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This review presents the scope of research presented in an October 2016 lecture pertaining to the award of the 2015 Max Bergmann Medal. The advancement in synthetic and biosynthetic chemistry as applied to the discovery of novel macromolecular drug candidates is reviewed.The evolution of the technology from the design, synthesis, and development of the first biosynthetic peptides through the emergence of peptide-based incretin agonists that function by multiple biological mechanisms is exemplified by the progression of such peptides from preclinical to clinical study. A closing section highlights recent progress made in total chemical synthesis of insulin and related peptides.

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“…Over the last decade, considerable effort has been devoted towards developing CE-based methods to characterize physiochemical protein properties such as M r , pI, pK a and dissociation constants [1]. More recently, methods based on ME (an evolutionary annexe of CE) for [12].…”

Section: Technological Statusmentioning

confidence: 99%

“…Almost a quarter century has passed since the first recombinant pharmaceutical protein was approved by the United Kingdom, Germany and the United States [1]. This achievement spawned from an insatiable demand for insulin from the limited stocks of beef and pork pancreatic glands supplied by the meat industry at the time.…”

Section: Introductionmentioning

confidence: 99%

“…This achievement spawned from an insatiable demand for insulin from the limited stocks of beef and pork pancreatic glands supplied by the meat industry at the time. World wide today recombinant insulin is used by more than 2 million [1] of the more than 170 million people suffering from the disease (http://www.who.int/diabetes/en/) and as of 2004 there were ten new biotechnology products to fight diabetes in the development pipeline (2004 Survey: Medicines in Development, Biotechnology, http://www. phrma.org) [2].…”

Section: Introductionmentioning

confidence: 99%

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Electrophoresis of pharmaceutical proteins: Status quo

Little

Paquette²,

Roos

2006

Electrophoresis

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The biotechnology industry has undergone rapid growth in recent years largely due to the development and success of protein-based therapeutics for a wide range of disorders. Similar to traditional pharmaceuticals, characterization of a therapeutic protein for its physicochemical properties, process monitoring and lot release is crucial. Electrophoresis in the slab-gel format has and continues to be a mainstay of the protein laboratory; and more recently, CE has begun to make significant inroads for protein analysis in industrial settings. This review focuses on the electrophoresis of proteins with an emphasis on protein-based therapeutics in the capillary, slab-gel and to a lesser extent, the microchip format. Reported applications of electrophoresis at several stages of the biopharmaceutical industry covering the period of 2000-2005 will be discussed.

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The trials and tribulations of producing the first genetically engineered drug

Abstract: Fifty years ago, the determination of the structure of DNA sparked a genetic revolution. Here, I give a personal perspective of the challenges involved in the development of the first biological therapeutic resulting from this revolution: recombinant human insulin.

Cited by 19 publications

References 0 publications

Insulin structure and function

Insulin structure and function

Max Bergmann award lecture:Macromolecular medicinal chemistry as applied to metabolic diseases

Electrophoresis of pharmaceutical proteins: Status quo

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