The UK is a Leader in Preclinical Cell and Gene Therapy Research
The UK has a rich and diverse range of preclinical research and is setting the foundations for the therapies of the future. the CGT catapult’s recently published preclinical research database indicates continued expansion of these trends
As a centre of translational excellence in the UK, the CGT Catapult is progressing a portfolio of projects with the UK and international communities. The UK preclinical research database is a valuable tool for tracking cell and gene therapy trends and enables us to plan activities appropriately and identify needs for the sector going forward. The purpose of the database is to be a tool for academics, commercial organisations and investors operating in the cell and gene therapy space and to demonstrate the rich science base in the UK. It also provides an indication of the likely future directions of cell, gene and other advanced therapies.
A large volume of data projects was collected across a wide range of therapeutic agents and disease areas. The technology readiness level of the projects captured varies from early-stage research to projects in which clinical trials are expected to be undertaken in the coming years.
Here is an overview of the main findings of the database and the preclinical research being undertaken in the UK.
The preclinical research that has been identified this year covers a broad range of disease areas. Oncological studies (including both haematological malignancies and solid tumours) are the most frequent at over 100 projects, closely followed by neurological disorders, also with over 100 projects. Additional significant activity is seen in ophthalmology, cardiovascular disease and orthopaedics. Figure 1 provides more detail of the range and numbers of research programmes.
Figure 1. Disease areas studied in UK preclinical projects in 2017
Therapeutic Delivery Method
Not only is there a vast range of disease areas being addressed in the UK, there are a wide assortment of therapeutic cell types being investigated. Figure 2 illustrates the types of therapeutic delivery methods being used and provides a further breakdown of the individual cell and viral vector types.
The most widely used delivery method is tissue specific/stem progenitor cells at 36%, which is due to the diversity of projects that utilise these types of cells, including ophthalmology, neurological disorders and gastroenterological disorders studies.
The second most widespread delivery method is MSCs/stromal cells, which are most commonly used to develop therapies targeting cardiovascular and orthopaedic conditions.
Approximately 11% of the preclinical programmes in the UK use in vivo gene therapies whose utility includes the study into cardiovascular disease, cancer, haemophilia and conditions of the eye.
Pluripotent stem cells were found to comprise around 13% of the therapies studied and are similarly diverse with respect to the disease area to which they are applied. Although, their use is more frequently investigated in early-stage translational research.
Figure 2. Therapeutic delivery methods investigated in preclinical research in 2017x
The heat map in Figure 3 provides details of the various funding sources supporting preclinical advanced therapy research in the UK and the disease areas that these organisations are targeting. The identified preclinical projects are supported by a wide range of funding organisations and from private investment. With regards to the number of projects funded, the Medical Research Council (MRC) is the most prolific funding body providing grants to nearly 140 projects including both preclinical studies and earlier translational research work (Figure 4).
Figure 3. Heatmap demonstrating the funding sources for preclinical research by disease area
The majority of late-stage projects currently receive funding through EU grants. However, the following organisations also support late-stage projects: Innovate UK, MRC, The British Heart Foundation and the Wellcome Trust. Figure 4 gives a further analysis of this preclinical research funding landscape by looking at the number of studies funded by each organisation.
In recent years, the number of studies utilising gene modification techniques has increased as the industry better understands and improves these methods; this trend will likely continue into the future.
The majority of projects did not use gene modification techniques but a growing number are. 77 projects were identified in which gene modification was utilised. However, it is probable that the actual figure is considerably higher and this discrepancy is explained by the difficulty in capturing this type of project information through the methodology used.
On the whole, lentiviral gene modification is the predominant technique with 26 studies reported. There were 13 reported instances of retroviral modification and, interestingly, 19 reported cases of CRISPR-Cas 9 usage. However, it should be noted that the bulk of cases where CRISPR-Cas 9 was being used were in projects in the early stages of development.
Figure 5 illustrates the overall findings of the usage of gene modification techniques for both ex-vivo and in vivo gene therapy applications.
Figure 5. Instances of gene modification techniques used in the identified preclinical projects in 2017