Dr Rafael J. Yáñez-Muñoz

Personal profile

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Rafael J. Yáñez-Muñoz BSc PhD FHEA

Reader in Advanced Therapy 

Advanced Gene and Cell Therapy laboratory (AGCTlab.org), School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, UK

Rafael Yáñez is a Reader in the Centre for Biomedical Sciences at the School of Biological Sciences, Royal Holloway-University of London, UK. Dr Yáñez previously held Lecturer appointments with King’s College London and University College London, and received his PhD and BSc in Biochemistry and Molecular Biology from the Autonomous University of Madrid, Spain. Dr Yáñez has a strong interest in research translation, and extensive experience in gene and cell therapy for both common and rare diseases. He is particularly involved in the development of safer methods, using genome editing (listen to a BBC5 live interview) and viral vectors modified to avoid integration in the cellular genome. His latest research is of relevance to neurodegenerative and inherited diseases, including spinal muscular atrophy, spinal injury, Parkinson disease, immunodeficiencies and Duchenne muscular dystrophy. Dr Yáñez is the Treasurer of the British Society for Gene and Cell Therapy and a trustee of the Genetic Alliance UK.

[Rare Disease Dancer picture credits: design, Ramiya Lakshman; stylisation, Andrea Yáñez-Cunningham]



08 Jun 2016 - Rafael writes blog on new research on mitochondrial donation for the British Society for Gene and Cell Therapy.
24 May 2016
- Rafael gives a seminar at the Institute of Child Health, University College London.
07 May 2016
- Rafael completes 71-mile Ride Scorpion cycle in support of The SMA Trust, raising £2,700. Thank you sponsors!
26 Apr 2016 - Rafael participates in debate on Genome Editing Technology - The Ethical and Regulatory Viewpoint at BioTrinity.
25 Apr 2016 - Interested in a career in science? Read Spinal Muscular Atrophy Support UK's Q&A interview with Rafael.
29 Feb 2016We run our 6th Rare Disease Day @ Royal Holloway event, hosting 100 secondary school students.
14 Jan 2016 - Our review paper on Genome Editing for monogenic diseases is published in Molecular Therapy.
01 Jan 2016 - Our UK SMA Research Consortium, for collaborative work on Spinal muscular atrophy, kicks-off.


Rare Disease is hot on the agenda!

3,000,000. That is the number of people in England who will be affected by a rare disease in their lifetime. 20% of the Health budget will go to look after them, mostly providing symptomatic and palliative care, because there are hardly any curative treatments. And we have not started talking about the relatives who will have to stop working and become full-time carers…

How is that possible if they are rare diseases? Well, there are 6,000-8,000 of them (we do not even have an accurate number!), and even though each disease affects fewer than 1 in 2,000 people, taken together they are a massive issue.

So why are rare diseases hot on the agenda? Because slowly but finally there is widespread understanding of their importance. Countries are developing Rare Disease National Plans (see the recently published UK National Strategy for Rare Diseases, which will provide the basis for the National Plans in the UK Nations). International collaboration, always important in research but critical in the case of rare diseases, has allowed the creation of an International Rare Disease Research Consortium (IRDiRC), with declared goals of developing diagnostic methods for most rare diseases and treatments for 200 of them by 2020. And Gene and Stem Cell Therapy research has finally provided some curative treatments, with many more in the pipeline.

Is the job done? By no means. It still takes five years for some people to be properly diagnosed, the care for most people affected is far from optimal, and in most cases there is no curative treatment. Raising awareness is critical, and that is the goal of Rare Disease Day, an annual international awareness day celebrated the last day of February (because on a leap year it is a rare day!). Dr Yáñez organises a yearly event to mark Rare Disease Day (RDD@RHUL).


RDD2015 banner


Other links:

All publications (in PubMed)

Rare Disease research: a personal journey (Royal Holloway Let's Talk about disability lecture series, 29th Oct 2014, Yáñez slideshow)

Have you heard of Same but Different? It is a beautiful photography project on rare disease


Teaching (restricted to Royal Holloway):

BS3590 (Molecular Basis of Inherited Disease)
BS3530 (Advanced Molecular Biology: Regulation and Manipulation of Eukaryotic Genes)
UK SMA Research Consortium (2016-2018; Spinal Muscular Atrophy)
CHASE-IT (2013-2016; Coordinator; Chondroitinase ABC for Spinal Injury Therapy)
PERSIST (2009-2013; Novel Tools for Gene and Cell Therapy)
NEUGENE (2008-2012; Gene Therapy for Parkinson Disease)
GENAME (2007-2010; Targets and Therapeutics for Spinal Muscular Atrophy)

CLINIGENE (2006-2011; joined in 2007; Gene Therapy Network)


UK SMA RC.jpg  CHASE-IT logo.jpg   PERSIST logo.jpg   NEUGENE logo.jpgGENAME logo.jpgCLINIGENE logo.jpg

Recent publication highlight:
Boza-Morán, M., Martínez-Hernández, R., Bernal, S., Wanisch, K., Also-Rallo, E., Le Heron, A., Alías, L., Denis, C., Girard, M., Yee, J.-K., Tizzano, E.F. and Yáñez-Muñoz, R.J. (2015) Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons. Sci Rep 5, 11696. doi:10.1038/srep11696. [PubMed]
We have observed a progressive reduction of SMN and PLS3 proteins during differentiation of induced pluripotent stem cells to motor neurons, similar to some reports in animals and some controversial data from human development. These changes may underpin the susceptibility of motor neurons to spinal muscular atrophy. We now will investigate the reason for the changes, and more importantly, progress our research for novel therapies taking these protein changes into account. The research also shows how we are trying to reduce reliance on animal experiments whenever possible, as these stem cells now allow the production of human cells that cannot be obtained directly from patients and we can study the cells in lab dishes. Please see the Press Release and Research News. This paper is in the top 5% of all research outputs tracked by Altmetric.

Research interests


Overview of current research

Our laboratory works on gene and cell therapy for common and rare (mostly inherited) diseases. Our main interest lies in the development of safer methods relying on either genome editing (aka genome surgery or gene repair) or episomal vectors. We mostly use novel, integration-deficient lentiviral vectors and adeno-associated viral vectors. Using genome editing we are developing treatments for the rare primary immunodeficiencies and Duchenne muscular dystrophy. Using episomal vectors we are particularly interested in the treatment of spinal muscular atrophy, spinal injury (both of which are rare diseases) and Parkinson disease. We have also converted the non-replicating integration-deficient lentivector episomes into replicating episomes of wider applicability. Haematopoietic stem cells and induced pluripotent stem cells (iPSCs) are our preferred stem cell models.


Too obscure? Try the lay description below instead.


Join us!  [MPhil/PhD]  [Postdocs]


Labelling of neurons with integration-deficient lentiviral vectors. A vector expressing eGFP (a gene that makes cells fluoresce green) was used to mark cells in the spinal cord (left) or the olfactory bulb in the brain (right). On the left panel motor neurons were also stained red with an antibody, so if these cells have taken up the viral vector the overlap of red and green fluorescence in their cell bodies is seen as yellow.


Why use episomal lentivectors?

Many gene therapy strategies require transduction (genetic modification with a viral vector) of somatic stem cells, neurons or other cells which divide rarely or do not divide at all. HIV belongs to a class (Genus) of viruses called Lentivirus, which in turn are part of a wider Family called Retroviridae, or more commonly, retroviruses. Lentiviruses distinguish themselves from other retroviruses in several ways, including their ability to cross the nuclear membrane, which allows them to infect cells that are not dividing. However, in common with other retroviruses, lentiviruses integrate their genome into the chromosomes of the cells they infect. Retroviral and lentiviral vectors likewise integrate into the genome of the transduced cells, which can lead to unwanted effects on the genes at or near the integration site, something called insertional mutagenesis. In the worst-case scenario such negative events can lead to cancer. Furthermore, each transduced cell will have the vector integrated at a different chromosomal location, which may affect or not vector gene expression. This can cause differences in vector gene expression in different cells, what we call position effect variegation. It has long been known that lentiviral vectors can be made integration-deficient using integrase mutations, but previously observed gene expression levels in vivo were very poor in the absence of integration.


Generation of episomal lentivector circles. The linear double stranded DNA vector molecule produced by standard lentivectors either integrates in the cellular genome or is converted into viral episomes. Higher levels of viral episomes are produced if integration is prevented through the use of mutations affecting the viral integrase.


Effective gene therapy with episomal lentivectors

We originally demonstrated that lentiviral (HIV) vectors modified to prevent integration in the cellular genome (so-called integration-deficient lentiviral vectors or IDLVs) are very efficient tools for gene therapy (Yáñez-Muñoz et al., 2006). We render the vectors integration-deficient by using missense mutations altering the integrase active site. Failing to integrate in the host cell genome these lentivectors generate increased levels of episomal vector circles, which lack replication signals and get diluted out through cell division. Gene expression from the viral episomes is transient in dividing cells but long-lived and efficient in quiescent tissues, including eye, brain, spinal cord and muscle (Yáñez-Muñoz et al., 2006; Hutson et al., 2012a,b; Peluffo et al., 2013; Lu-Nguyen et al., 2014; Lu-Nguyen et al., 2015). The main advantages of these non-integrating lentivectors in gene addition strategies are their highly reduced risk of causing insertional mutagenesis and their avoidance of position effect variegation.


Effective gene expression and therapy with non-integrating lentivectors in vivo. (Left) Integration-defective lentivector encoding eGFP was injected subretinally in adult mice. The image shows eGFP fluorescence in the fundus of the eye 9 months post-injection. (Right) RPE65-encoding lentivector was injected subretinally in RPE65-deficient mice. The electroretinograph shows electrical activity in the retina of the treated eye (but not in the contralateral eye) three weeks post-injection, indicative of the prevention of retinal degeneration caused by RPE65 deficiency (Courtesy of Prof Robin Ali).


Genome editing

Lentiviral episomes can also be used as platforms for cassettes designed for site-specific (Moldt et al., 2008) or homologous recombination (Rocca et al., 2014) with the cellular genome. These strategies allow targeting of such cassettes to safe havens where no cellular genes will be negatively affected by the insertion event. Homologous recombination (gene targeting) can also be used for genome editing, the ideal form of gene therapy for rare inherited diseases, in which the endogenous gene is repaired (Yáñez and Porter, 1998; Popplewell et al., 2013; Rocca et al., 2014; Prakash et al., 2016). The inventors of gene targeting received the 2007 Nobel Prize in Physiology or Medicine. The development of designer nucleases (most famously CRISPR-Cas, but also meganucleases, zinc-finger nucleases and TALENs; Prakash et al., 2016) which can cut the target gene and thus greatly boost the frequency of homologous recombination, has been a determining event to make gene repair a credible therapeutic strategy. In some cases, even the destruction of a gene by nuclease-only genome editing can provide a therapeutic benefit, exemplified by the clinical trials exploring destruction of the HIV CCR5 co-receptor in T-cells. The nuclease genes can also be delivered to cells using lentiviral episomes.


Correction of a mutation by gene repair. A corrective vector carrying genomic DNA with wild-type sequence undergoes homologous recombination with the mutant gene, resulting in the correction of the genetic mutation (orange lollipop). The corrected gene is expressed under physiological regulation from its endogenous locus.


Replicating lentiviral episomes

The episomal lentiviral circles do not have replication sequences and in proliferating cells they are progressively lost by dilution as the cell population expands. This makes them good vectors for transient gene expression in dividing cells, where they can provide a moderate expression level. We have recently patented and published a method in which a modification of culture conditions at the time of integration-deficient lentivector transduction allows efficient establishment of replicating episomes of wider applicability, in a collaborative project with Prof George Dickson (Kymäläinen et al., 2014).


Transient gene expression by integration-deficient lentiviral vectors in proliferating cells. HeLa cells were transduced at the indicated multiplicity of infection (MOI, vector copies/cell) with integration-proficient (int+) or integration–deficient (int-) lentivector expressing eGFP. The percentage of green cells at the indicated times was determined by flow cytometry. Similar percentages of transduction were achieved at 3 days post-transduction regardless of integration proficiency. Transduction percentages with non-integrating vector decline progressively as the cell population expands.


Research interests (continued)


Research group

Dr Jamuna Selvakumaran - jamuna.selvakumaran@rhul.ac.uk
Daphne Jackson Trust Fellow, sponsored by BBSRC. Project title: iPSC-based CNS models

Ms Neda Ali Mohammadi Nafchi (PhD student) - Neda.AliMohammadiNafchi.2012@live.rhul.ac.uk
Funded by Royal Holloway, University of London. Project title: Gene therapy for spinal muscular atrophy

Miss Versha Prakash (PhD student) - Versha.Prakash.2007@live.rhul.ac.uk
Funded by Royal Holloway, University of London. Project title: Prkdc gene surgery

Mr Mohammed Abdelrasul (PhD student) - Mohammed.Abdelrasul.2012@live.rhul.ac.uk
Funded by Egyptian Consulate. Project title: Reducing residual integration of IDLVs

Ms Sahar Akbari Vala (PhD student) - Sahar.AkbariVala.2013@live.rhul.ac.uk
Project title: Replicating lentiviral episomes

Mr Marc Moore (PhD student) - Marc.Moore.2010@live.rhul.ac.uk
Funded by Muscular Dystrophy Campaign (PI and main supervisor: Prof George Dickson). Project title: Safe harbour genome surgery for Duchenne muscular dystrophy

Mr Pradeep Harish (PhD student) - Pradeep.Harish.2013@live.rhul.ac.uk
Funded by Royal Holloway, University of London (PI and main supervisor: Prof George Dickson). Project title: Inhibition of myostatin for therapy in Duchenne muscular dystrophy


Past group members and their current destinations

Dr Klaus Wanisch – R&D Systems, UK

Dr Martin Broadstock – King’s College London, UK

Dr Céline Rocca – The Scripps Research Institute, USA

Dr Sherif G Ahmed – Harvard University, USA

Dr Tiziana Rossetti – Imperial College, UK

Dr María Gabriela Boza – Executive MBA in Management of Technology, Lausanne, Switzerland

Dr Ngoc Lu-Nguyen – Royal Holloway, University of London, UK

Dr Hanna Kymäläinen - Autolus Limited, UK 



All publications [PubMed]

Selected publications - Reviews and Commentaries

Prakash, V., Moore, M. and Yáñez-Muñoz, R.J. (2016) Current progress in therapeutic gene editing for monogenic diseases. Mol Ther 24, 465-474. Epub 2016 Jan 14. doi:10.1038/mt.2016.5. [PubMed]


Hutson, T.H., Foster, E., Moon, L.D.F. and Yáñez-Muñoz, R.J. (2013) Lentiviral vector-mediated RNA silencing in the CNS. Hum Gene Ther Methods 25, 14-32. Epub 2013 Nov 1. doi:10.1089/hgtb.2013.016. [PubMed]


Broadstock, M. and Yáñez-Muñoz, R.J. (2012) Challenges for gene therapy of CNS disorders and implications for Parkinson’s disease therapies. Hum Gene Ther 23, 340-343. Epub 2012 Apr 10. doi:10.1089/hum.2012.2507. [PubMed]


Wanisch, K. and Yáñez-Muñoz, R.J. (2009) Integration-deficient lentiviral vectors: a slow coming of age. Mol Ther 17, 1316-1332. doi:10.1038/mt.2009.122. [PubMed]


Yáñez, R.J. and Porter, A.C.G. (1998). Therapeutic gene targeting. Gene Ther 5, 149-159. [PubMed]


Selected publications - Primary papers

Lu-Nguyen, N.B., Broadstock, M. and Yáñez-Muñoz, R.J. (2015) Efficient expression of Igf-1 from lentiviral vectors protects in vitro but does not mediate behavioral recovery of a Parkinsonian lesion in rats. Hum Gene Ther, 26, 719-733. Epub 2015 Oct 1. doi: 10.1089/hum.2015.016. [PubMed]


Boza-Morán, M., Martínez-Hernández, R., Bernal, S., Wanisch, K., Also-Rallo, E., Le Heron, A., Alías, L., Denis, C., Girard, M., Yee, J.-K., Tizzano, E.F. and Yáñez-Muñoz, R.J. (2015) Decay in survival motor neuron and plastin 3 levels during differentiation of iPSC-derived human motor neurons. Sci Rep 5, 11696. Epub 2015 Jun 26. doi:10.1038/srep11696. [PubMed]


Cordero-Llana, O., Houghton, B., Rinaldi, F., Taylor, H., Yáñez-Muñoz, R.J., Uney, J.B., Fong-Wong, L. and Caldwell, M.A. (2014) Enhanced efficacy of the CDNF/MANF family by combined intranigral overexpression in the 6-OHDA rat model of Parkinson’s disease. Mol Ther 23, 244-54. Epub 2014 Nov 5. doi: 10.1038/mt.2014.206. [PubMed]


Negro-Demontel, M.L., Saccardo, P., Giacomini, C., Yáñez-Muñoz, R.J., Ferrer-Miralles, N., Vazquez, E., Villaverde, A. and Peluffo, H. (2014) Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy. Mol Ther Meth Clin Dev 1, 14047. Epub 2014 Oct 15. doi:10.1038/mtm.2014.47. [PubMed]


Rocca, C.J., Abdul-Razak, H.H., Holmes, M.C., Gregory, P.D. and Yáñez-Muñoz, R.J. (2014) A Southern blot protocol to detect chimeric nuclease-mediated gene repair. Methods Mol Biol 1114, 325-38. doi: 10.1007/978-1-62703-761-7_21. [PubMed]


Bartus, K., James, N.D., Didangelos, A., Bosch, K.D., Verhaagen, J., Yáñez-Muñoz, R.J., Rogers, J.H., Schneider, B.L., Muir, E.M. and Bradbury, E.J (2014) Large-Scale Chondroitin Sulfate Proteoglycan Digestion with Chondroitinase Gene Therapy Leads to Reduced Pathology and Modulates Macrophage Phenotype following Spinal Cord Contusion Injury. J Neurosci, 34, 4822– 4836. Epub 2014 Apr 2. doi: 10.1523/JNEUROSCI.4369-13.2014. [PubMed]


Lu-Nguyen, N.B., Broadstock, M. Schliesser, M, Bartholomae, C.C., von Kalle, C., Schmidt, M. and Yáñez-Muñoz, R.J. (2014) Transgenic expression from integration-deficient lentiviral vectors is neuroprotective in a rodent model of Parkinson Disease. Hum Gene Ther 25, 631-641. Epub 2014 Mar 18. doi:10.1089/hum.2014.003. [PubMed]


Kymäläinen, H., Appelt J.U., Giordano F.A, Davies A.F., Ogilvie C.M., Ahmed, S.G., Laufs, S., Schmidt, M., Bode, J., Yáñez-Muñoz, R.J., and Dickson, G. Long-term episomal transgene expression from mitotically stable integration-deficient lentiviral vectors (IDLVs) (2014) Hum Gene Ther, 25, 428-442. Epub 2014 Feb 2. doi:10.1089/hum.2013.172. [PubMed]


Popplewell, L., Koo, T., Leclerc, X., Duclert, A., Mamchaoui, K., Gouble, A., Mouly, V., Voit, T., Pâques, F., Cédrone, F., Isman, O., Yáñez-Muñoz, R.J. and Dickson, G. Gene correction of a Duchenne muscular dystrophy mutation by meganuclease-enhanced exon knock-in (2013) Hum Gene Ther 24, 692-701. Epub 2013 June 21. doi: 10.1089/hum.2013.081. [PubMed]


Peluffo, H., Foster, E., Ahmed, S.G., Lago, N., Hutson, T., Moon, L., Yip, P., Wanisch, K., Caraballo-Miralles, V., Olmos, G., Lladó, J., McMahon, S.B. and Yáñez-Muñoz, R.J. (2013) Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord. Gene Ther 20, 645-657. Epub 2012 Oct 18. doi: 10.1038/gt.2012.78. [PubMed]


Daboussi, F., Zaslavskiy, M., Poirot, L., Loperfido, M., Gouble, A., Guyot, V., Leduc, S., Galetto, R., Grizot, S., Oficjalska, D., Perez, C., Delacôte, F., Dupuy, A., Chion-Sotinel, I., Le Clerre, D., Lebuhote, C., Danos, O., Lemaire, F., Oussedik, K., Cédrone, F., Epinat, J.-C., Smith, J., Yáñez-Muñoz, R.J., Dickson, G., Popplewell, L., Koo, T., VandenDriessche, T., Chuah, M.K., Duclert, A., Duchateau, P. and Pâques, F. (2012) Chromosomal context and epigenetic mechanisms control the efficacy of genome editing by rare-cutting designer endonucleases. Nucleic Acids Res 40, 6367-6379. Epub 2012 Jun 15. doi:10.1093/nar/gks268. [PubMed]


Hutson, T.H., Foster, E., Dawes J.M., Hindges, R., Yáñez-Muñoz, R.J. and Moon, L.D.F. (2012b) Lentiviral vectors encoding shRNAs efficiently transduce and knockdown LINGO-1 but induce an interferon response and cytotoxicity in CNS neurons. J Gene Med 14, 299-315. Epub 2012 Apr 12. doi: 10.1002/jgm.2626. [PubMed]


Hutson, T.H., Verhaagen, J., Yáñez-Muñoz, R.J. and Moon, L.D.F. (2012a) Corticospinal tract transduction: a comparison of seven adeno-associated viral vector serotypes and a non-integrating lentiviral vector. Gene Ther, 19, 49-60. Epub 2011 May 12. doi:10.1038/gt.2011.71. [PubMed]


Zhao, R.-R., Muir, E.M., Alves, J.-N., Rickman, H., Allan, A.Y., Kwok, J.C., Roet, K.C.D., Verhaagen, J., Schneider, B.L., Bensadoun, J.-C., Ahmed, S.G., Yáñez-Muñoz, R.J., Keynes, R.J., Fawcett, J.W., Rogers, J.H. (2011) Lentiviral vectors express Chondroitinase ABC in cortical projections and promote sprouting of injured costicospinal axons. J Neurosci Methods 201, 228-238. Epub 2011 Aug 9. [PubMed]


Bartholomae, C.C., Arens, A., Balaggan, K.S., Yáñez-Muñoz, R.J., Montini, E., Howe, S.J, Paruzynski, A., Korn, B., Appelt, U., MacNeil, A., Cesana, D., Abel, U., Glimm, H., Naldini, L., Ali, R.R., Thrasher, A.J., von Kalle, C. and Schmidt, M. (2011) Lentiviral vector integration profiles differ in rodent postmitotic tissues. Mol Ther., 19, 703-10. Epub 2011 Mar 1. [PubMed]


Yip, P.K., Wong, L.-F., Sears, T.A., Yáñez-Muñoz, R.J. and McMahon, S.B. (2010) Neuronal calcium sensor 1 promotes functional plasticity after unilateral spinal cord injury. PLoS Biology, Jun 22;8(6):e1000399, Epub 2010 June 22. doi: 10.1371/journal.pbio.1000399. [PubMed]


Gabriel, R., Eckenberg, R., Paruzynski, A., Bartholomae, C.C., Nowrouzi, A., Arens, A., Howe, S.J., Recchia, A., Cattoglio, C., Wang, W., Faber, K., Schwarzwaelder, K., Kirsten, R., Deichmann, A., Ball, C.R., Balaggan, K.S., Yáñez-Muñoz, R.J., Ali, R.R., Gaspar, H.B., Biasco, L., Aiuti, A., Cesana, D., Montini, E., Naldini, L., Cohen-Haguenauer, O., Mavilio, F., Thrasher, A.J., Glimm, H., von Kalle, C., Saurin, W. and Schmidt, M. (2009) Comprehensive genomic access to vector integration in clinical gene therapy. Nat Med 15, 1431-1436. doi:10.1038/nm.2057. [PubMed]


Moldt, B., Staunstrup, N.H., Jakobsen, M., Yáñez-Muñoz, R.J. and Mikkelsen, J.G. (2008) Site-directed genomic insertion of lentiviral DNA circles. BMC Biotech 8: 60.doi:10.1186/1472-6750-8-60. [PubMed]


Yáñez-Muñoz, R.J., Balaggan, K.S., MacNeil, A., Howe, S., Schmidt, M., Smith, A.J., Buch, P., MacLaren, R.E., Anderson, P.N., Barker, S., Duran, Y., Bartholomae, C., von Kalle, C., Heckenlively, J.R., Kinnon, C., Ali, R.R. and Thrasher, A.J. (2006) Effective gene therapy with nonintegrating lentiviral vectors. Nat. Med. 12, 348-353. doi:10.1038/nm1365. [PubMed]


Key collaborators

Genome Editing:

Dr Philip Gregory and Dr Michael Holmes (Sangamo Biosciences, Inc, USA)

Prof Adrian Thrasher and Dr Steven Howe (Institute of Child Health, University College London)

Dr Juan Antonio Bueren (CIEMAT, Spain)

Prof George Dickson (Royal Holloway)


Spinal Muscular Atrophy:

UK SMA Research Consortium

GENAME consortium

Dr Simon Waddington (University College London)


Spinal injury:

CHASE-IT consortium: Dr Liz Bradbury (Wolfson CARD, King’s College London), Dr Joost Verhaagen (Netherlands Institute for Neuroscience), Dr Liz Muir (University of Cambridge).

Dr Lawrence Moon (Wolfson CARD, King’s College London)


Parkinson Disease:

NEUGENE consortium


Multipotential stem cells:

Dr Mathilde Girard (iSTEM, France)

Dr Sarah Thomas (King’s College London)


Reduction of IDLV integration:

Dr Rik Gijsbers (University Leuven, Belgium)


Replicating episomes:

Prof George Dickson (Royal Holloway)


Vector integration:

Dr Manfred Schmidt and Prof Dr Christof von Kalle (National Centre for Tumor Diseases, Germany)

Research sponsors

Association Française contre les Myopathies



Daphne Jackson Trust

European Union (FP7)

Genoma España and FundAME (GENAME project)



SMA Trust

Spinal Research


The Friends of Guy's Hospital


British Society for Gene and Cell Therapy: http://www.bsgct.org
European Society of Gene and Cell Therapy: http://www.esgct.org
American Society of Gene & Cell Therapy: http://www.asgct.org
Sociedad Española de Terapia Génica y Celular: http://www.setgyc.es (in Spanish)

Lay description

Medicine has little to offer against many diseases, and this is particularly true in the case of neurodegenerative and inherited disorders, most of which are rare diseases (affecting fewer than 1 in 2,000 people). Gene and cell therapy is a relatively new field of biomedical research that is attempting to address this need by developing a new breed of pharmaceuticals based on nucleic acids (DNA, RNA and artificial derivatives). The idea is that the activity of our genes (or the genes of organisms that infect us) can be manipulated using designer nucleic acids to modify the relevant cells in our bodies, and in that way cure, ameliorate or slow down disease. As our cells are very efficient at preventing the entry of nucleic acids, scientists need to develop tools to introduce them by stealth. Viruses are very good at bringing their genes into cells, so scientists have learned to hijack viruses: they remove all the pathogenic viral genes (which cause disease) and replace them with the designer genes that they want to use for treatment. By doing this they produce viral vectors, which currently are the most efficient way to deliver nucleic acids to cells.

Many different viruses have been converted into viral vectors, and our laboratory mostly works on gene therapy with vectors derived from HIV, the lentivirus causing AIDS. In addition to removing HIV’s pathogenic (which cause the disease) genes, we make lentiviral vectors even safer by preventing them from inserting their DNA into the cellular chromosomes. This stops our vectors from affecting cellular genes in ways that could cause cancer. We are using these novel lentivectors to develop therapies for the rare spinal muscular atrophy (a progressive inherited disease affecting neurons in the spinal cord) and spinal injury, and the more common Parkinson disease (a progressive disorder in which specific brain neurons die). For these diseases we are using non-integrating lentiviral vectors to introduce extra genes that we believe may have a beneficial effect. However, for many genetic diseases the ideal treatment would be gene repair of the faulty gene inside the cell, something that can be achieved by doing genome editing (the inventors of such targeted gene modification received the 2007 Nobel Prize in Physiology or Medicine). We are using genome editing to repair the faulty gene that causes a form of severe combined immunodeficiency (a disease of the immune system that makes patients unable to fight infections) and the gene causing Duchenne muscular dystrophy (a degenerative neuromuscular disease first affecting mobility and later breathing and the heart).

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