A synthetic biology approach for consistent production of plant-made recombinant polyclonal antibodies against snake venom toxins

Antivenoms developed from the plasma of hyperimmunized animals are the only effective treatment available against snakebite envenomation but shortage of supply contributes to the high morbidity and mortality toll of this tropical disease. We describe a synthetic biology approach to affordable and cost-effective antivenom production based on plant-made recombinant polyclonal antibodies (termed pluribodies). The strategy takes advantage of virus superinfection exclusion to induce the formation of somatic expression mosaics in agroinfiltrated plants, which enables the expression of complex antibody repertoires in a highly reproducible manner. Pluribodies developed using toxin-binding genetic information captured from peripheral blood lymphocytes of hyperimmunized camels recapitulated the overall binding activity of the immune response. Furthermore, an improved plant-made antivenom (plantivenom) was formulated using an in vitro selected pluribody against Bothrops asper snake venom toxins and has been shown to neutralize a wide range of toxin activities and provide protection against lethal venom doses in mice.Fil: Julve Parreño, Jose Manuel. Universidad Politécnica de Valencia; EspañaFil: Huet, Estefanía. Universidad Politécnica de Valencia; EspañaFil: Fernández del Carmen, Asun. Universidad Politécnica de Valencia; EspañaFil: Segura, Alvaro. Universidad de Costa Rica; Costa RicaFil: Venturi, Micol. Universidad Politécnica de Valencia; EspañaFil: Gandía, Antoni. Universidad Politécnica de Valencia; EspañaFil: Pan, Wei-Song. Universidad Politécnica de Valencia; EspañaFil: Albaladejo, Irene. Universidad Politécnica de Valencia; EspañaFil: Forment, Javier. Universidad Politécnica de Valencia; EspañaFil: Pla, Davinia. Instituto de Biomedicina de Valencia; EspañaFil: Wigdorovitz, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; ArgentinaFil: Calvete, Juan J.. Instituto de Biomedicina de Valencia; EspañaFil: Gutiérrez, Carlos. Universidad de Las Palmas de Gran Canaria; EspañaFil: Gutiérrez, José María. Universidad de Costa Rica; Costa RicaFil: Granell, Antonio. Universidad Politécnica de Valencia; EspañaFil: Orzáez, Diego. Universidad Politécnica de Valencia; Españ

Tucumanin, a β-hydroxy-γ-lactone bistetrahydrofuranic acetogenin from Annona cherimolia, is a potent inhibitor of mitochondrial complex I

A new β-hydroxy-γ-methyl-γ-lactone bistetrahydrofuranic acetogenin, tucumanin, with the infrequent symmetrical threo/trans/threo/trans/ threo relative configuration at the tetrahydrofuran rings was isolated from Annona cherimolia (Annonaceae) seeds. The inhibitory potency on the mitochondrial complex I of acetogenins with this relative configuration (tucumanin and asimicin) was compared with that shown by the corresponding pairs with an asymmetrical threo/trans/threo/trans/erythro relative configuration (laherradurin/rolliniastatin-2, and itrabin/molvizarin). All these compounds act as selective inhibitors of mitochondrial complex 1 in the 0.18 - 1.55 nM range.Fil: Barrachina, Isabel. Universidad de Valencia; EspañaFil: Neske, Adriana. Universidad Nacional de Tucumán; ArgentinaFil: Granell, Susana. Universidad de Valencia; EspañaFil: Bermejo, Almudena. Universidad de Valencia; EspañaFil: Chahboune, Nadia. Universidad de Valencia; EspañaFil: El Aouad, Noureddine. Universidad de Valencia; EspañaFil: Alvarez, Olga. Universidad Nacional de Tucumán; ArgentinaFil: Bardon, Alicia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina. Universidad Nacional de Tucumán; ArgentinaFil: Zafra Polo, M. Carmen. Universidad de Valencia; Españ

Higgs pair production in the MSSM with explicit CP violation

In the minimal supersymmetric standard model with explicit CP violation, associated production of the lightest Higgs boson with heavier ones is analyzed. Due to explicit CP violation, the Higgs bosons are no longer CP eigenstates so that both of the heavy Higgs bosons contribute to the process. While the radiative corrections in the Higgs sector turn out to be quite important, the vertex radiative corrections remain small as in the CP conserving theory.Comment: 5 pp, 5 figs, Talk at Valencia 99, Valencia, Spain, May 3-8, 199

CP Violation in Λ\Lambda to p π−\pi^-: SM vs New Physics

I discuss CP violation in $\Lambda$ to p $\pi^-$ comparing the standard model expectations with what could happen in new physics scenarios. I point out that Fermilab experiment E871 is sensitive to some of these scenarios.Comment: 6 pages, Talk at Hyperon 99 Fermilab, and at Symmetries in Subatomic Physics, Adelaide, 200