Computational models of the
ribozyme's internal motions allowed the researchers to capture and understand the finer details of the fast-paced reaction.
A hammerhead
ribozyme, based on the Haseloff and Gerlach model (9) was designed to cleave a pGUA sequence at nucleotide 5910 within the HIV genomic clone NL43 (Accession number M19921) (Figure 1).
This includes selectively inhibiting viral transcription (64), or by using antisense constructs (65-67),
ribozymes (68-70), or short-interfering RNA (siRNA) (71-74), which lead to the degradation of the E6/E7 mRNAs.
Ribozyme's creation was facilitated in part by the University of Colorado's Technology Transfer Office, through which the company licensed Cech's CU-held patents in its effort to commercialize them for use in human therapeutics.
There is an exceptionally strong calcium-binding site, at which barium or strontium (or even magnesium) competes (the
ribozyme is inactivated).
Fourth, attempts to enhance the limited catalytic properties of RNA molecules in so-called
ribozyme engineering experiments have inevitably required extensive investigator manipulation, thus demonstrating, if anything, the need for intelligent design, not the efficacy of an undirected chemical evolutionary process.
Not only did the
ribozymes go about their business of building RNA strands, but the reactions continued for much longer in the icy test tubes than at higher temperatures, the team reports.
Several in vitro and in vivo studies show effective targetting of high-risk HPVs using antiviral
ribozymes and antisense molecules, siRNA and shRNA (Table III).
Targeting sites within HIV-1 cDNA with a DNA-cleaving
ribozyme. Biochemistry 1996;35:11693-701.
In the presence of the appropriate template RNA and nucleoside triphosphates, the
ribozyme extends an RNA primer by the successive addition of up to six mononucleotides.
Previously, Dr Cowens worked in senior medical positions at Genomic Health, held senior product development positions at Chiron (now Novartis Vaccines & Diagnostics) and
Ribozyme Pharmaceuticals as well as worked as an oncology consultant for IDEC Pharmaceuticals, Scios and Ligand Pharmaceuticals.
Holliger, "Ribozyme-Catalyzed Transcription of an Active
Ribozyme," Science 322 (2011): 209-12.