Designing a Hammerhead Ribozyme
Which Discriminates between bcr/abl Fusion Transcripts of Chronic Myelogenous Leukemia (CML)
& bcr Transcripts of Normal Cells

Ribozymes (RNA enzymes) are catalytic antisense RNA molecules that act as enzymes. Ribozymes act as ribonucleases that cleave RNA molecules in a sequence-specific manner. Therapeutic applications of ribozymes include the inhibition of viral replication in somatic cells (e.g. HIV, Influenza A), as well as, the specific inactivation of gene products (e.g. oncogenes). Engineering of ribozyme-mediated viral resistance in plants constitute one of the major applications in agriculture.

We are designing and synthesizing several hammerhead ribozymes capable of cleaving the bcr/abl fusion mRNA expressed in chronic myeloid leukemia (CML) patients. Using molecular biology techniques, we are changing the ribozyme sequence/structure in order to investigate its specificity, activity and in vivo stability. Elucidating the kinetic and thermodynamic factors that affect the ribozyme-substrate reaction is also underway.

OBJECTIVES

•  Producing ribozymes that can be used to cleave oncogenic RNA transcripts in CML patients.

ACHIEVEMENTS

•  Ribozymes were prepared and cleavage is being characterized.