Intellectual Property Rights and Vaccines.

Over the past 20 years, there has been steady, year-on-year growth in the number of granted vaccine-related patents. It is therefore important that those involved in vaccine research should be aware of both the risks and opportunities that patents create. The aim of this chapter is to offer a brief introduction to how, and when, patent rights might become available to vaccine developers and to explain the potential risk of infringement of third-party patent rights and the potential consequences.This chapter begins with a brief introduction to the patent application process and the international patent systems. The advantages and drawbacks of patent protection are discussed, followed by an overview of patent infringement and the various legal safe-harbors that may be available for certain research activities. Other features of the patent system which may be of particular relevance in the vaccines context are also discussed, such as compulsory licensing, sovereign states' rights to use patented inventions and voluntary technology sharing agreements. The chapter concludes with a discussion of the SARS-CoV-2 (COVID-19) pandemic and recent developments in the field of vaccine patents that have arisen as part of the international response.

A nonsense exon in the Tpm1 gene is silenced by hnRNP H and F.

As well as generating protein isoform diversity, in some cases alternative splicing generates RNAs that harbor premature termination codons and that are subject to nonsense-mediated decay (NMD). We previously identified an apparent pseudo-exon in the rat alpha-tropomyosin (Tpm1) gene as a probable genuine alternatively spliced exon that causes NMD when spliced into Tpm1 RNA. Here, we report the analysis of cis-acting splicing regulatory elements within this "nonsense exon." Guided by the data set of predicted splicing enhancer and silencer elements compiled by Zhang and Chasin, we made a series of mutations through the nonsense exon and found that like authentic exons it is densely packed with enhancer and silencer elements. Strikingly, 11 of 13 tested mutations behaved as predicted computationally. In particular, we found that a G-rich silencer at the 5' end, which is crucial for skipping of the nonsense exon, functions by binding hnRNP-H and F.

Gene loops juxtapose promoters and terminators in yeast.

Mechanistic analysis of transcriptional initiation and termination by RNA polymerase II (PolII) indicates that some factors are common to both processes. Here we show that two long genes of Saccharomyces cerevisiae, FMP27 and SEN1, exist in a looped conformation, effectively bringing together their promoter and terminator regions. We also show that PolII is located at both ends of FMP27 when this gene is transcribed from a GAL1 promoter under induced and noninduced conditions. Under these conditions, the C-terminal domain of the large subunit of PolII is phosphorylated at Ser5. Notably, inactivation of Kin28p causes a loss of both Ser5 phosphorylation and the loop conformation. These data suggest that gene loops are involved in the early stages of transcriptional activation. They also predict a previously unknown structural dimension to gene regulation, in which both ends of the transcription unit are defined before and during the transcription cycle.