Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver

Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models. Here we describe the generation of four putative P. falciparum LA-GAPs, generated by CRISPR/Cas9-mediated gene deletion. One out of four gene-deletion mutants produced sporozoites in sufficient numbers for further preclinical evaluation. This mutant, Pf Delta mei2, lacking the mei2-like RNA gene, showed late liver growth arrest in human liver-chimeric mice with human erythrocytes, absence of unwanted genetic alterations and sensitivity to antimalarial drugs. These features of Pf Delta mei2 make it a promising vaccine candidate, supporting further clinical evaluation. Pf Delta mei2 (GA2) has passed regulatory approval for safety and efficacy testing in humans based on the findings reported in this study.</p

The BaBar silicon vertex tracker

The silicon vertex tracker (SVT) for the BaBar experiment at the PEP-II asymmetric B factory is a 5-layers device based on double sided, AC coupled silicon strip detectors. It is read out by a custom IC, the AToM chip, that can simultaniously acquire, digitze and transmit data. The main purpose of the SVT is to accurately measure the decay position of the B mesons that are produced, which is essential for extracting CP asymmetries. Here, we report on the SVT design as well as progress on its fabrication and assembl

An integrated encyclopedia of DNA elements in the human genome.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research