Human Molecular Genetics, Vol 7, 1649-1653, Copyright © 1998 by Oxford University Press
LA Phylactou, MW Kilpatrick and MJ Wood
The discovery that RNA can act as a biological catalyst, as well as a
genetic molecule, indicated that there was a time when biological reactions
were catalysed in the absence of protein-based enzymes. It also provided
the platform to develop those catalytic RNA molecules, called ribozymes, as
trans -acting tools for RNA manipulation. Viral diseases or diseases due to
genetic lesions could be targeted therapeutically through ribozymes,
provided that the sequence of the genetic information involved in the
disease is known. The hammerhead ribozyme, one of the smallest ribozymes
identified, is able to induce site-specific cleavage of RNA, with ribozyme
and substrate being two different oligoribonucleotides with regions of
complementarity. Its ability to down-regulate gene expression through RNA
cleavage makes the hammerhead ribozyme a candidate for genetic therapy.
This could be particularly useful for dominant genetic diseases by
down-regulating the expression of mutant alleles. The group I intron
ribozyme, on the other hand, is capable of site-specific RNA trans
-splicing. It can be engineered to replace part of an RNA with sequence
attached to its 3' end. Such application may have importance in the repair
of mutant mRNA molecules giving rise to genetic diseases. However, to
achieve successful ribozyme-mediated RNA-directed therapy, several
parameters including ribozyme stability, activity and efficient delivery
must be considered. Ribozymes are promising genetic therapy agents and
should, in the future, play an important role in designing strategies for
the therapy of genetic diseases.
REVIEWS
Ribozymes as therapeutic tools for genetic disease
Department of Human Anatomy, Oxford University, South Parks Road, Oxford OX1 3QX, UK. leonidas.phylactou@anat.ox.ac.uk
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