Oligonucleotide, antibody and peptide therapeutics--from design to the clinic.
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Antibodies, Monoclonal↗
Biomedical subjects
John Goodchild
Publications and source records attributed to John Goodchild.
Oligonucleotide therapeutics: 25 years agrowing.
The year 2003 saw the 25th anniversary of the first publication of research using antisense oligonucleotides in cells. Oligonucleotides complementary to RNA use a variety of mechanisms to provide a direct link from genomics to gene function, drug target validation and new lead therapeutics. Other applications use oligonucleotides that bind to DNA or proteins to serve similar purposes. In this review, recent advances in mechanisms, chemical modifications and uses of oligonucleotides are discussed, and a broad overview of progress, mainly concerning RNA inhibition, is provided.
ATP-Binding Cassette Transporters↗
Hammerhead ribozymes for target validation.
Expensive failures in the pharmaceutical industry might be avoided by target validation at an early stage. Often, the full consequences of inhibiting a chosen drug target do not emerge until late in the development process. One option is to use hammerhead ribozymes as highly specific ribonucleases targeted exclusively at the mRNA encoding the target protein. The first part of this review is concerned with the mechanism and design of hammerhead ribozymes. This includes the chemistry of their action, specificity of cleavage and ability to discriminate between different mRNAs and selection of suitable cleavage sites. In considering their use for target validation, hammerhead ribozymes are divided into two categories. Endogenous ribozymes are transcribed inside the cell where they act whilst exogenous are introduced into the cell from outside. Exogenous ribozymes are synthesised chemically and must be protected against cellular nucleases. Information is provided on transfection methods and vectors that have been used with endogenous ribozymes as well as synthesis and chemical modification of exogenous ribozymes. Of proteins inhibited in cells or whole organisms, those in animal experiments are emphasised. Comparisons are made with other approaches, especially the use of antisense oligonucleotides or RNA.
Animals↗