Enhancing mRNA stability through the addition of stabilizing untranslated regions

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 20).Messenger-RNA (mRNA) therapy, in which mRNA is introduced to cells or tissues to cause a transient expression of specific genes, has applications ranging from tissue engineering to neural regeneration. This transient nature of mRNA, however, limits the duration of gene upregulation, and potentially reduces the efficacy of mRNA therapy. In this paper, various mRNA constructs were studied to identify stable designs which could be used for long-lasting mRNA therapies. Specifically, the GFP gene was prepared with four different hemoglobin untranslated regions (UTR's), which are known for their stabilization effects on mRNA. Each mRNA template was created through the digestion and ligation of a cDNA template, reversed transcribed from total RNA, and transfected into fibroblasts. The resulting fluorescence was measured as a surrogate for translation efficiency and duration. It was determined that the human beta-globin B UTR resulted in a fluorescence level that was tenfolds brighter than human alpha-globin 1 (HBA1), which was the least effective stabilizing untranslated region. This highlights the importance of UTR selection for future mRNA therapies.by Thi Tran.S.B

Molecular Kondo effect in flat-band lattices

The Kondo effect of a single magnetic impurity embedded in the Lieb lattice is studied by the numerical renormalization group. When the band flatness is present in the local density of states, it quenches the participation of all dispersive electrons in the Kondo singlet formation, and reduces the many-body Kondo problem to a two-electron molecular Kondo problem. The two-electron analog of the many-body Kondo singlet, a quantum entanglement of two spins, is stable at low temperature, and the impurity contributions to thermodynamical and dynamical quantities are qualitatively different from that obtained in the conventional Kondo effect in systems without flat bands. The existence conditions of the molecular Kondo effect in narrow band systems are also discussed

ORGANOCHLORINATED PESTICIDES IN THE AQUATIC ENVIRONMENT AT THE ESTUARIES AND IN TAM GIANG-CAU HAI LAGOON OF THUA THIEN HUE PROVINCE FROM 2005 TO 2007 : I. STATUS OF ORGANOCHLORINATED PESTICIDES IN THE WATER AND SEDIMENT

Joint Research on Environmental Science and Technology for the Eart