Author: Fco. Javier Molina Estévez

Aarhus University Summer Course Completes Two Weeks of Intensive CRISPR/Cas9 Teaching

GeneHumdi in collaboration with Aarhus University (AU) is proud to announce the successful conclusion of a magnificent two-week summer course: Genetic Engineering using CRISPR/Cas. This initiative coordinated by Rasmus O. Bak provides a comprehensive program supporting transformative learning experiences for 34 students who hailed from a diverse array of educational backgrounds and where 14 different nations were represented. The course took participants on a deep dive into the world of CRISPR/Cas, equipping them with invaluable insights and skills that will undoubtedly shape their academic and professional journeys.

This summer course has been previously featured in the AU summer agenda, but this is the first time that GeneHumdi has partnered with the prestigious Aarhus University to promote the education of students interested in Medical Genome Editing applications.

Throughout the course, participants were guided through a series of learning objectives designed to foster a robust understanding of the CRISPR/Cas technique and its broad applications. Students delved into the core principles that underpin CRISPR/Cas technology, gaining a solid foundation in its mechanisms and potential, and were offered with a comprehensive overview of CRISPR/Cas technology’s current status and its relevance within the dynamic landscape of biomedical research. Participants gained insights into its potential to revolutionize various fields within healthcare and scientific discovery. Participants were equipped with the ability to critically evaluate and select relevant parameters for gene editing projects. This encompassed the selection of appropriate CRISPR platforms, cell types, delivery methods, and vector design strategies.

This course nurtured their skills to discern and interpret outcomes from diverse assays used to quantify both on- and off-target gene editing. This analytical competency is crucial for ensuring accurate and effective gene editing outcomes. Later, attendants were encouraged to independently conceptualize and execute CRISPR/Cas gene editing projects. This practical experience empowered them to translate theory into real-world applications.

The course pomotes enabling students to navigate and analyze original literature within the CRISPR/Cas field. This skill not only strengthens their understanding but also allows them to formulate pertinent research hypotheses based on current scientific discourse. The participants’ diverse educational backgrounds encompassed fields ranging from Medicine, Molecular Medicine, and Biotechnology, to Nanoscience, Dentistry, Biology, and Bioinformatics. This rich blend of perspectives and expertise enriched the course’s collaborative learning environment.

The GeneHumdi organization joins local organizing extending their sincere gratitude to its dedicated team members – Sofie, Kasper, Sujan, Simon, and Sabina – whose invaluable support greatly enhanced the exercises and group projects. Special recognition is also extended to Emil and Sarah for their engaging lectures that deepened participants’ grasp of the subject matter.

This year AU’s Summer Course was made even more impactful through collaboration with the EU COST network in Genome Editing for the treatment of humans diseases, GeneHumdi | COST action CA21113. This COST Action funded travel scholarships for nine deserving students, exemplifying the commitment to democratizing access to cutting-edge education in Europe.

The involvement of the COST network also facilitated the incorporation of lectures by esteemed international gene editing experts. The AU Summer University extends its sincere appreciation to the following COST members for their contributions to nurturing the next generation of scientific leaders:

The collaboration with the COST network proved instrumental in enhancing the course’s impact, enabling the inclusion of lectures delivered by international gene editing experts, members of GeneHumdi. They brought their knowledge and experience to the AU Summer University’s platform, enriching the learning experience for the participating students, and increasing the multicultural experience. Notable lectures and discussion were held by Yonglun Luo (Alun) from Denmark, Anna Cereseto from Italy, Julian Grünewald from Germany, Ayal Hendel from Israel, Raul Torres, Javier Molina Estévez from Spain, and Karim Benabdellah (the later three from Spain). Their contributions are an embodiment of the commitment to fostering the growth of the next generation of scientific leaders.

This Aarhus University partnership with the COST network underscores it’s dedication to providing a global and collaborative educational experience. By bringing together accomplished professionals and emerging talents, this initiative contributes to the advancement of knowledge and the cultivation of a dynamic scientific community that transcends geographical boundaries.

GeneHumdi is a pioneering European initiative, highlights the commitment to harnessing Genome Editing for Clinical Practice. By uniting professionals from basic science to end-point healthcare, the initiative aims to harmonize introduction and implementation of genome editing practices, helping to better understand their scientific basis, practical application, and raise awareness about their potential to rectify disease-causing genes.

For further information about the Aarhus Summer University and its transformative CRISPR/Cas summer course, please reach out to Rasmus O. Bak. at Aarhus University or Javier Molina at GeneHumdi.

The Spanish Gene and Cell Therapy Society (SETGyC) is a sound and long running organization comprising dedicated Spanish researchers committed to the research and development of gene transfer and cell modification for clinical purposes. The SETGyC maintains strong connections with industrial and regulatory partners. The society embraces a collaborative spirit that aligns perfectly with the principles of our GeneHumdi initiative. In a heartfelt open letter, the current President of SETGyC, Ander Izeta, emphasizes that “the foundation of cutting-edge medical advancements lies in the utilization of novel therapeutic tools such as gene therapy and genome editing for the treatment of genetic disorders.” Reflecting the shared valued of this institution with our owns.

This year, Pamplona will host over a hundred leading gene therapy scientists, including renowned key speakers. Tony Cathomen , Felipe Prosper, Ignacio Melero, Paula Rio , Juan Bueren and Raúl Torres to name a few of the the forefront of gene therapy and genome editing for therapeutic purposes in Europe that are presenting in this meeting.

To promote the Action’s mission dr. K. Benabdel lah has been awarded a grant by the GeneHumdi Management Committee to facilitate the dissemination and presentation of the Genome Editing for the treatment of Human disease (GeneHumdi | COST action CA21113) during the Bi-annual Meeting of the Spanish Society of Gene and Cell Therapy. This grant aims to support Dr. Benabdel lah in showcasing the remarkable achievements and advancements of the GeneHumdi initiative to all attendees at the conference.

During his speech in the inaugural session, Karim Benabdellah had the opportunity to present the ambitious plan of GeneHumdi. He graciously extended an invitation to early-career professionals and students to join the initiative, recognizing that nurturing relationships and fostering communication and collaboration with specialists from across Europe is a crucial initial step.

Furthermore, reinforcing the presence of GeneHumdi and to reach young scientist at the SETGyC meeting, the GeneHumdi initiative has a dedicated sign-in stand, where our extraordinaire Grand Holder Coordinator, Maria J. Bazuelo, is actively engaging with prospective Action Members. She is sharing our values and her insight into the mission of the initiative and highlighting the remarkable opportunities that come with being part of this transformative action.

The first wave of scientific articles produced thanks to interactions within our GeneHumdi network is out

The GeneHumdi Network aims to pave pathways between the key stages for medical development: basic and translational research, development, production, and healthcare providers and regulators to secure that patients really benefit to the use Gene Editing approaches able to change the actual fate of many diseases.

The goal is ambitious and the first step is to nurture relationships to promote communication and unification of criteria among specialist all over Europe. In this regard, the past March the network held a in person meeting in Granada (Spain) to favor interactions between the members. We are please to witness that this interactions are starting to fruit in the form of joint scientific articles.

Cartoon illustrating gene editing techniques commonly used in academic research. In this example, engineered nucleases are employed to make targeted cuts at specific sequences in the chromosomal DNA. These cuts allow researchers or clinicians to introduce desired changes or reverse disease-causing mutations. Image courtesy of K. Benabdellah, adapted “High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting NewWorld Full of Challenges and Opportunities“

The first article fruit of the GeneHumdi network funded by the COST (European Coordination in Science and Technology) appeared in April, shortly after the first Action Meeting. It as a review “The Black Hole: CAR T Cell Therapy in AML” focused on Chimeric Antigen Receptor T (CAR T) lymphocytes used in innovative therapies.

In the review the authors tackle the fact that researchers have struggled to make progress in adoptive cellular therapies for acute myeloid leukemia (AML) compared to B cell cancers. Trials using chimeric antigen receptor (CAR) T cells have shown limited response rates and side effects. New approaches are needed.

Graphical Abstract of the review: “The Black Hole: CAR T Cell Therapy in AML“

Authors discuss the challenges of CAR T cells and other therapies in AML. The genetic and molecular diversity in AML makes treatment complex. Single-cell sequencing data provided insights into cellular variations and hierarchies in AML. While promising strategies include advanced CAR T, TCR-T, and CAR NK therapies, personalized microenvironment targeting, and allogeneic approaches, efforts continue to enhance adoptive cellular therapies for AML by understanding its complexities and exploring innovative strategies.

Two GeneHumdi Action members collaborated to write this review: Erden Atilla (GENyO center, Spain) and Karim Benabdel lah (GENyO center, Spain) were opening the door for many more join articles from the network.

In May this year, a second article from signed from members of the GeneHumdi Network was published in Frontiers of Immunology under the title “Failure of ALL recognition by CAR T cells: a review of CD 19- negative relapses after anti-CD 19 CAR-T treatment in B-ALL”.

In this review the authors address the use of CAR-T cell therapy, which has greatly improved the outlook for patients with refractory or relapsed B cell acute lymphoblastic leukemia (B-ALL), a condition with a poor prognosis under conventional treatment. With anti-CD19 CAR-T cell therapy, the chances of event-free survival for these patients have significantly increased to 50-60% at 1.5 years, which is a significant advancement for this severely ill group. While over 70 % patients achieve complete remission (They defeat the blood cancer until the point is not clinically detectable), the main challenge remains the relapse of the disease (the comeback of tiny amounts of cancer cells that survived and escape detection in the first place and reproduce the disease). Both clinical trials and real-world evidence have shown that relapses often occur due to the limited expansion or persistence of CAR-T cells. Surprisingly, even when CAR-T cells are functioning adequately, some tumor cells manage to evade their attack, resulting in a relapse without the CD19 antigen.

Graphical abstract of the review “Failure of ALL recognition by CAR T cells: a review of CD 19- negative relapses after anti-CD 19 CAR-T treatment in B-ALL” by Aparicio-Pérez C. et al.

The text highlights various mechanisms that contribute to the escape of leukemic cells, including acquired mutations, alternative splicing of the CD19 antigen, loss or masking of the CD19 epitope, leukemia lineage switching, and trogocytosis (this last is when a cell nibbles another cell). In this comprehensive review, authors analyze these mechanisms, examine the incidence of CD19-negative relapse in clinical trials and real-world evidence, and provide an update on the current understanding of the situation.

The review is signed by several GeneHumdi authors in a thrilling collaboration between Clinicians and academic to help promote the actions values: Maria Dolores Carmona(IMIBIC Institute, Spain), Karim Benabdel lah (GENyO center, Spain) and Concha Herrera (Reina Sofía University Hospital, Spain).

Last but not least, the first international publication nurtured from GeneHumdi Network interactions highlight the need to apply Gene Editing for treatment of Humans diseases.

The review “High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting NewWorld Full of Challenges and Opportunities” signed by  2 Members of the Action: Karim Benabdellah and Kyriakos E. Kypreos.

In this paper they review te role of  High-density lipoprotein (HDL), a type of fat and protein in the blood that helps remove excess cholesterol. It also plays a role in metabolic disorders like obesity, diabetes, and fatty liver disease. Low levels of HDL and dysfunctional HDL are found in certain cancers. Adjusting HDL levels and improving its function can benefit these conditions. Previous attempts to raise HDL cholesterol (HDL-C) through medications were not successful, and new clinical trials are needed. Gene editing technology may revolutionize treatment by improving dysfunctional HDL.

Cartoon cortesy of K. Benabdel lah extracted from “High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting NewWorld Full of Challenges and Opportunities“.

These articles are proof that Gene Editing for the treatment of humans Editing Network is set in motion and already having an impact promoting bounds among Academic and Clinical peers. We expect more articles to be produce to help unify scatter information regarding the Genome Tools and strategies available to help treat Human disease as the action further promotes dialogue and unification between peers and among the different actors and agencies involved in new medicines discovery, development, authorization and manufacture.

Gene Editing for the treatment of Humans Diseases (GeneHumdi | CA21113) is funded by the EU through Cooperation in Science and Technology (COST)
Granada , 2023

References:

(1) Atilla, E.; Benabdellah, K. The Black Hole: CAR T Cell Therapy in AML. Cancers 2023, 15, 2713. https://doi.org/10.3390/cancers15102713

(2) Zvintzou, Evangelia, Eva Xepapadaki, George Skroubis, Victoria Mparnia, Katerina Giannatou, Karim Benabdellah, and Kyriakos E. Kypreos. 2023. “High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities” Pharmaceuticals 16, no. 6: 855. https://doi.org/10.3390/ph16060855

(3) Aparicio-Pérez C, Carmona M, Benabdellah K and Herrera C (2023) Failure of ALL recognition by CAR T cells: a review of CD 19-negative relapses after anti-CD 19 CAR-T treatment in B-ALL. Front. Immunol. 14:1165870. doi: 10.3389/fimmu.2023.1165870