Genomics


Genetically-engineered models: the value of precious GEMs


Genetically-engineered animal models (GEMs) are critical tools for drug discovery and development, but intellectual property (IP) concerns can complicate access. As pharma and biotech increasingly outsource R&D activities to universities, careful scrutiny is required to ensure adherence to IP restrictions on research tools across those collaborative activities. As demonstrated by recent high-profile lawsuits, the stakes are higher than ever for all parties.


By Dr Megan M. MacBride


D


espite improvements to in vitro assays, animal models are a critical part of pre- clinical drug discovery and development


and will remain so for the foreseeable future. In particular, GEMs are specialised reagents with value across R&D stages. These tools often have significant upfront costs to generate and charac- terise, but awareness of their value for research and/or commercial applications, and of the intel- lectual property associated with GEMs, may vary among researchers, particularly in academia.


What are GEMs? GEMs are animals which have a genetic alteration artificially introduced by humans. Most commonly these are mice and rats, but advances in transgenic technology over the past decade have made possi- ble the development of genetically-engineered zebrafish, pigs and even non-human primates. Examples of genetic alterations carried by GEMs are gene deletions, added sequences such as reporter genes, or replacement of a native gene with the human version. A wide variety of tech- niques exist to make GEMs, and quite sophisticat- ed mutations can be made. According to the


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International Mouse Strain Resource (IMSR), more than 200,000 genetic modifications have been made in mouse embryonic stem cells, so the number of existing GEMs across all animal species and transgenic technology types is significant. Over time, use of GEMs has increased signifi-


cantly, with the proportion of standard strains (non-genetically-engineered normal laboratory ani- mals) used falling. While standard strains remain widely used, GEMs permit different types of exper- iments. For example, when it comes to develop- ment of biologic drugs, GEMs with humanised tar- get proteins can permit study of the human drug rather than use of a surrogate in preclinical studies. Data from the UK Home Office compiled by the organisation Understanding Animal Research demonstrates this trend toward greater use of GEMs and decreased use of standard strains (Figure 1).


From freely shared to strings attached Unlike some other types of research tools, GEMs are self-propagating. A single breeding pair of genetically-engineered mice can start a colony which produces scores of mice within just a few


Drug Discovery World Fall 2018


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