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Recombinant interferon - the 20th anniversary

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Recombinant Protein Drugs

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

In the summer of 1977 at a Gordon Conference I took my annual walk with Peter Lengyel, and, as he described the complexities of the mode of action of mouse IFN and of the control of its expression, it became evident that cloning of the chromosomal IFN gene would lead to a wealth of information unattainable by any other means. Moreover, the undertaking was a challenge, since pure IFN was extremely hard to come by, its structure was unknown and would probably not be elucidated for years to come, no good antibodies to IFN were known to be available, and the mRNA was presumably present at a very low level. However, as Peter explained to me, there did exist a very sensitive assay for IFN mRNA: the injection of about 50 ng of poly(A)+ RNA from IFN-producing cells into each of a dozen Xenopus oocytes led to synthesis of easily measurable amounts of IFN [1]. It occurred to me that an assay for cloned IFN cDNA might be based on a hybridisation procedure in connection with this IFN mRNA assay (see Figs 1 and 2). Assume you already possess an IFN cDNA clone and that you immobilise the denatured DNA on a solid support such as a Millipore filter. If this filter is annealed with poly(A)+ RNA containing IFN mRNA and then washed, you would expect it to retain the IFN RNA but none of the other mRNAs. If the filter is subsequently heated in water, the RNA-DNA hybrids will be denatured and the IFN mRNA can be washed off and assayed for in the oocyte test. If any other hybrid cDNA is attached to the filter

Article Footnote

When asked to contribute an essay on the cloning of interferon (IFN) alpha, I decided to update an article entitled “The Cloning of Interferon and Other Mistakes” (In: I Gresser (ed.): Interferon I. Academic Press, London and New York, 101-134)which I had written 1981, at a time when the events were still fresh in my mind. I left the original text largely unchanged, but added retrospective comments in the form of footnotes and appended a summary of some developments following the writing of the original article.

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Weissmann, C. (2001). Recombinant interferon - the 20th anniversary. In: Buckel, P. (eds) Recombinant Protein Drugs. Milestones in Drug Therapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8346-7_1

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  • DOI: https://doi.org/10.1007/978-3-0348-8346-7_1

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