Gene editing medicines

07 - 08 November 2024 09:00 - 17:30 Online Free Watch online
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Abstract 3d DNA molecule helix on a blue background

This meeting will explore the innovations that are transforming the future of gene editing medicines.

Just 12 years after the discovery of CRISPR/Cas9, the first gene editing medicines have been approved and many more are in clinical development. This meeting will explore the innovations that are transforming gene editing medicines and their impact on patient health.

The potential applications of gene editing technologies for treating diseases are beginning to be realised. The science underpinning gene editing medicines continues to develop at a rapid pace, and clinical applications are growing. However, challenges in terms of manufacturing, scale-up, regulation, equitable access, health economics and safety make the widespread roll-out of these medicines difficult. 

This two-day conference will discuss recent advances, future priorities, and the wider social and economic context for the application of gene editing approaches in a healthcare setting.

Transforming our future conferences

This conference forms part of the Royal Society's industry-focused Transforming our future series. These unique meetings feature cutting-edge science and bring together experts from industry, academia, healthcare settings, funding bodies, the wider scientific community and government to explore and address key scientific and technical challenges of the coming decade.

Organisers

  • Steve Rees

    Steve Rees

    Steve Rees is Senior Vice-President of Discovery Sciences at AstraZeneca with responsibility for the discovery of novel drug candidates, using multiple therapeutic modalities, for projects for all AstraZeneca therapy areas. Prior to his current appointment Steve held positions of increasing responsibility at AstraZeneca including leadership of the Discovery Biology and Screening Sciences and Sample Management departments. He has served as Chair of the European Laboratory Research and Innovation Group, Chair of the European Council of the Society of Laboratory Automation and Screening and as Industry Trustee of the British Pharmacological Society and is a member of  the Royal Society Science, Industry and Translation Committee. Steve was awarded an OBE by Her Majesty the Queen in 2021 for services to science and the COVID19 response.

  • Laura Sepp-Lorenzino

    Laura Sepp-Lorenzino

    Laura Sepp-Lorenzino, Ph.D. joined Intellia Therapeutics in 2019 as Chief Scientific Officer and is responsible for Research and Early Development. Intellia is harnessing CRISPR-based technologies to revolutionize the future of medicine. Laura previously held leadership positions at Vertex, Alnylam and Merck. She serves on the Board of Directors of Taysha Gene Therapies and the Alliance for Regenerative Medicine, and on the Scientific Advisory Boards for Thermo Fisher Scientific, the U.K. Nucleic Acid Therapies and Arsenal Capital Partners. She received her professional degree in Biochemistry from the University of Buenos Aires, Argentina, and both her M.S. and Ph.D. in Biochemistry from New York University.

  • Professor Robin Ali

    Professor Robin Ali

    Professor Robin Ali is Professor of Human Molecular Genetics at King’s College London and Director of KCL Centre for Gene Therapy and Regenerative Medicine. He is also Director of the KCL Gene Therapy Vector Facility. Robin is a Fellow of the Academy of Medical Sciences, NIHR Senior Investigator (Emeritus) and a recent past President of the European Society of Gene & Cell Therapy. The focus of his research is the development of gene and cell therapy for the treatment of retinal disorders; he is a founder and former Chief Scientific Officer of MeiraGTx PLC, a Nasdaq-listed clinical-stage gene therapy company. Robin Ali and members of his team have received numerous prizes for their work on developing new treatments for retinal degeneration, including the €1M Champalimaud Vison Award.

    Robin has published over 200 peer-reviewed papers with landmark papers and preclinical therapeutic proof-of-concept studies for many different ocular disorders. As chief investigator, he established the world’s first clinical trial of gene therapy for retinopathy and his group is now developing a first-in-human clinical trial of transplantation of ES-derived cone photoreceptors for the treatment of macular degeneration. 

  • Professor Waseem Qasim

    Professor Waseem Qasim

    Waseem Qasim is Professor of Cell and Gene Therapy at UCL Great Ormond Street (GOS) Institute of Child Health in London. He has led ‘bench-to-bedside’ development of new treatments that use emerging genome editing strategies to reprogram immune cells to treat cancers. Clinical studies at GOS were the first to show the potential of donor T cell modified, initially using TALENs and then CRISPR/Cas9 and, most recently, ‘base editing’ technology. Similar approaches are now being developed to repair genes inside living cells to help children with inherited blood or immune disorders, and these developments are setting the scene for a new generation of genetic medicines.

  • Robin Lovell-Badge

    Professor Robin Lovell-Badge FRS

    Robin Lovell-Badge obtained his PhD at University College London in 1978 and was a postdoc in Cambridge, both with Martin Evans. After an EMBO fellowship in Paris he established his independent laboratory in 1982 at the MRC Mammalian Development Unit, UCL, directed by Anne McLaren. In 1988 he moved to the MRC National Institute for Medical Research, which was incorporated into the Francis Crick Institute in 2015. In 1990, his lab discovered Sry, the Y-linked sex determining gene and the Sox gene family. Major themes of his past and current work include sex determination, development of the gonads, nervous system and pituitary, and the biology of stem cells within these systems. He is also very active in both public engagement and policy work. He has a strong interest in the prospects for applications of human genome editing and was on the organising committee for the three international Summits held on this, including as chair for the 2023 meeting.

Schedule

09:00-09:05 Welcome and opening remarks
Steve Rees

Steve Rees

AstraZeneca

09:05-09:25 CRISPR/Cas9-based in vivo gene editing for transthyretin amyloidosis
Professor Julian Gillmore

Professor Julian Gillmore

UCL

09:25-09:30 Q&A

Chair

Steve Rees

Steve Rees

AstraZeneca

09:30-09:35 Introduction to Session 1
Steve Rees

Steve Rees

AstraZeneca

09:35-09:55 CRISPR on Drugs: Pharmacological Enhancement of Genome Editing

The CRISPR-Cas9 system is a transformative tool for genome engineering, yet achieving efficient gene insertion and repair remains a critical challenge, particularly in slowly dividing cells. At AstraZeneca, we have focused on enhancing targeted gene integration through the application of small molecules that modulate double-strand break repair pathways. Employing a two-inhibitor strategy (2i), we significantly boost the outcomes of nuclease-dependent editing, increasing both precision and efficiency in gene repair. Using engineered proprietary nucleases encapsulated in lipid nanoparticles (LNP) and a novel AAV vector configuration, we have demonstrated effective in vivo gene repair in an animal model of homozygous familial hypercholesterolemia, highlighting the potential for therapeutic interventions.

Marcello Maresca

Marcello Maresca

AstraZeneca

09:55-10:15 Genetic engineering of hematopoietic stem cells to treat human disease: state-of-the-art and future perspective
Luigi Naldini

Luigi Naldini

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget)

10:15-10:30 Q&A

Chair

Laura Sepp-Lorenzino

Laura Sepp-Lorenzino

Intellia Therapeutics

11:00-11:05 Introduction to Session 2
Laura Sepp-Lorenzino

Laura Sepp-Lorenzino

Intellia Therapeutics

11:05-11:20 Multiplexed CRISPR-based cell engineering to generate persistent allogeneic solutions and improved function in solid tumors
Dr Birgit Schultes

Dr Birgit Schultes

Intellia Therapeutics

11:20-11:35 Programming gene expression by targeted epigenetic editing
Professor Angelo Lombardo

Professor Angelo Lombardo

San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) & Vita-Salute San Raffaele University

11:35-11:50 Delivery of genome editing tool kits in engineered lentivirus-derived particles

The invention of CRISPR/Cas gene editing tools offers hope for the development of drugs treating genetic defects directly in patients. However, delivering such tools to specific cells and organs remains a key challenge. Inspired by retroviruses' ability to carry integrase proteins into cell nuclei of infected cells, we engineered HIV-1-derived lentivirus-derived nanoparticles (LVNPs) to deliver transposases, designer nucleases, and RNA-guided endonucleases into cells. Recently, we demonstrated successful targeted DNA cleavage in cells treated with LVNPs loaded with SpCas9/guide RNA ribonucleoproteins (RNPs) and achieved gene editing via homology-directed repair, using reverse-transcribed DNA from co-packaged vector RNA as a template. The LVNP platform also supports base and prime editing, and pseudotyping enables cell-specific gene editing and adapted use in primary cells. Early in vivo evidence of LVNP-directed gene editing in the mouse retina fuels hope that LVNPs can be further developed and produced in large scale for therapeutic applications.

Professor Jacob Giehm Mikkelsen

Professor Jacob Giehm Mikkelsen

Aarhus University

11:50-12:05 Adeno-associated virus vectors
12:05-12:20 Lipid nanoparticles are enabling gene therapies

Lipid nanoparticles (LNPs) represent an advanced drug delivery system that is now enabling gene therapies. LNPs are critical to enabling the function of nucleic acids which are unable to access their target sites, the internal compartment of cells. The first-ever approved RNA interference therapeutic, Onpattro, was designed to deliver short interfering RNA to the liver to treat hereditary transthyretin amyloidosis. Further advancements of these systems through optimization of the LNP have enabled their use in the messenger RNA vaccines commercialized by Pfizer/BioNTech and Moderna. Most recently, LNPs have been applied to enable in vivo gene editing, protein replacement and to establish passive immunity. While substantial advancements have resulted in several medicines for liver diseases and vaccines, the critical barrier to treating or even curing disease is the ability to deliver nucleic acids to their target site in a precise manner to non-liver tissues.

Dr Jayesh Kulkarni

Dr Jayesh Kulkarni

NanoVation Therapeutics (NTx)

12:25-12:40 Q&A

Chair

Robin Lovell-Badge

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

13:45-13:50 Introduction to panel
Professor Robin Lovell-Badge FRS

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

13:50-15:00 Panellists
Sharmila Nikapota

Sharmila Nikapota

Cure EB Founder Trustee

Alyssa

Alyssa

Great Ormond Street Hospital Patient

Chair

Professor Waseem Qasim

Professor Waseem Qasim

UCL Great Ormond Street Institute of Child Health

15:30-15:35 Introduction to session 3
Professor Waseem Qasim

Professor Waseem Qasim

UCL Great Ormond Street Institute of Child Health

15:35-15:55 Precise gene correction for Primary Immunodeficiency Diseases

Inborn errors of immunity (IEIs) are monogenic disorders of immunity that causes significant morbidity or early mortality. Hematopoietic stem cell transplant can be life-saving but are limited by graft rejection, graft failure, graft-versus-host disease or a lack of suitably HLA-matched donors. Gene therapy using a patient’s own stem cells could mitigate these problems. The earliest stem cell gene therapy clinical trials using oncoretroviral vectors to insert therapeutic transgenes inadvertently activated nearby oncogenes and caused leukemias. Improved lentivectors used currently integrate in actively transcribed genes and can cause aberrant fusion transcripts.  Next-gen targeted gene editing tools like base editing provides precision and efficacy that should address random integration concerns and importantly, restores physiological gene expression. Preclinical base editing studies of a CYBB mutation in patient HSPCs confirming highly specific and efficient mutation repair supported our clinical gene therapy trial using BE HSPCs for treatment of Chronic Granulomatous Disease.  Our goal is to provide efficacy and safety data from treated patients to support extending the approach to other IEIs. 

Suk See De Ravin

Suk See De Ravin

National Institutes of Health

15:55-16:15 Hacking T cells to fight leukaemia

Most patients with leukaemia can be successfully treated with chemotherapy, but if the disease relapses and becomes ‘hard-to-treat’, we can now offer alternative approaches that harness powerful immune effects. T-cells, a critical group of white blood cells that protect us from infections, can be collected and reprogrammed to hunt down and eradicate certain types of blood cancer. Recently, genome editing technologies, including CRISRP/Cas9 and Base editing, have been used to simultaneously ‘hack’ multiple genes in T cells from healthy donors so that they can be pre-manufactured and used to treat different types of leukaemia without the need for any matching. These evolving gene-edited medicines offer powerful new therapies that are being tested in carefully designed clinical trials in children and adults.

Professor Waseem Qasim

Professor Waseem Qasim

UCL Great Ormond Street Institute of Child Health

16:15-16:35 Therapeutic gene editing for cardiovascular and metabolic diseases: from the leading cause of death to N-of-1 disorders
Professor Kiran Musunuru

Professor Kiran Musunuru

University of Pennsylvania

16:35-16:50 Q&A

Chair

Laura Sepp-Lorenzino

Laura Sepp-Lorenzino

Intellia Therapeutics

09:00-09:05 Welcome and opening remarks
Professor Robin Ali

Professor Robin Ali

King's College London

09:05-09:30 CRISPR Cures For All: an Actionable Path
Fyodor Urnov

Fyodor Urnov

University of California, Berkeley

Chair

Professor Robin Ali

Professor Robin Ali

King's College London

09:30-09:35 Introduction to session 1
Professor Robin Ali

Professor Robin Ali

King's College London

09:35-09:55 Innovation and challenges in CMC (Chemistry, Manufacturing and Controls) with new technology platforms – The gene and cell therapy case
Dafni Bika

Dafni Bika

AstraZeneca

09:55-10:15 Talk 2
Christopher Vann

Christopher Vann

Autolus Ltd

10:15-10:35 Talk 3
Vanessa Almendro Navarro

Vanessa Almendro Navarro

Danaher

10:35-10:50 Q&A

Chair

Robin Lovell-Badge

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

11:20-11:25 Introduction to session 2
Professor Robin Lovell-Badge FRS

Professor Robin Lovell-Badge FRS

The Francis Crick Institute

11:25-11:45 Casgevy: A case study in the global regulatory strategy and lessons learned from the journey to approval
Stephanie Krogmeier

Stephanie Krogmeier

Vertex Pharmaceuticals

11:45-12:05 Precision in Progress: Assessing and Mitigating Genotoxic Risks in Genome Editing
Professor Toni Cathomen

Professor Toni Cathomen

University of Freiburg

12:05-12:25 Talk 3
John Spoors

John Spoors

NICE

12:25-12:40 Q&A

Chair

Professor Robin Ali

Professor Robin Ali

King's College London

13:40-13:45 Introduction to session 3
Professor Robin Ali

Professor Robin Ali

King's College London

13:45-14:05 Talk 1
Professor Bobby Gaspar

Professor Bobby Gaspar

Orchard Therapeutics, UCL

14:05-14:25 Talk 2
Stefano Benvenuti

Stefano Benvenuti

Fondazione Telethon

14:25-14:45 Talk-3
14:45-15:00 Q&A