Neil Clarke - Articles and news items

Next generation antibody therapeutics: Antibody fragments, dual-targeting strategies, and beyond…

Issue 5 2009, Past issues / 9 October 2009 /

A multitude of novel therapeutic antibody formats based on modification of the conventional IgG format have arisen in recent years. The intensification of interest in this area reflects a pressing need for an additional repertoire of therapeutic molecules which retain the exquisite binding specificity and low intrinsic toxicity of monoclonal antibodies (mAbs), while engineering additional features which enhance clinical efficacy, for example, by improving tissue perfusion or demonstrating increased specificity for a defined cell type. This article briefly reviews the key molecular aspects of therapeutic antibody fragments in development, including single-chain Fv fragments (scFvs), camelid VHH domains, human domain antibodies (dAbs), and an expanding array of bispecific/dual-targeting variants. Such molecules, characterised by unique biophysical and pharmacological properties, are ideally placed to become the next generation of antibody-based therapeutics.

RNAi therapeutics: addressing targets?

Issue 4 2008, Past issues / 2 August 2008 /

Gene silencing by RNA interference (RNAi) uses double-stranded RNA to shut down gene expression in cells. This provides the possibility that this new methodology could be used in the treatment of disease symptoms and disease processes. A particular attraction of RNAi (as well as other gene knockdown methods of treatment, including antisense) is that, at present, no one class of protein appears to be refractive to silencing using this method and, therefore, it has the potential to make any gene product a target for pharmaceutical intervention. As will be discussed later though, delivery of these large polyanionic molecules to their site of action may pose a significant challenge.


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