GenScript Gene & Cell Engineering
Virtual Summit

July 22nd, 2021.
11:00AM – 6:00PM EDT

Gene and cell engineering advances have influenced almost all branches of life sciences. From the lab to the clinic, innovative gene synthesis technologies and gene editing tools have transformed basic, translational, and biomedical research. GenScript has partnered with pioneers pushing the boundaries in gene and cell engineering by providing its deep expertise in gene synthesis technologies. This first, GenScript Gene & Cell Engineering Virtual Summit will showcase cutting-edge research from leaders leveraging synthetic biology technologies in drug-discovery, de novo protein design, and genome-editing.

One Day of exceptional scientific sessions entirely online with free registration.

Engage and network with leaders in the field without travel hassles.

Learn about the latest discoveries, deep insights and visions for the future from experts in the field.

Earn continuing education credit (CEC).

Speakers

*Name in Alphabetical order

Alexander Marson, MD, PhD

Director, Gladstone-UCSF Institute of Genomic Immunology

Ben Kleinstiver, PhD

Assitant Professor, MGH, HMS- Center for Genomic Medicine

Gal Cafri, PhD

Immunotherapy and Genetic Engineering Group Leader, Sheba Medical Center

Alex Marson is Director of the Gladstone-UCSF Institute of Genomic Immunology and Associate Professor in the UCSF Department of Medicine, Division of Infectious Diseases. He serves as the scientific director for Human Health at the Innovative Genomics Institute (IGI) and is a member of the Parker Institute for Cancer Immunotherapy and a Chan Zuckerberg Biohub investigator. Work in Dr. Marson’s lab aims to understand the genetic programs controlling human immune cell function in health and disease, with an emphasis on developing and applying CRISPR genome engineering tools to primary immune cells, especially T cells. Combining genomics and gene editing approaches, the lab works to assess the consequences of coding and noncoding genetic variation on immune cell function and autoimmune disease risk and to genetically engineer human immune cells to target cancer, autoimmunity, and infectious diseases.

Ben Kleinstiver is a biochemist with interests in genome editing technology development and scalable protein engineering. He received his Ph.D in Biochemistry from the University of Western Ontario, and completed his postdoctoral studies at Massachusetts General Hospital and Harvard Medical School. Within the Center for Genomic Medicine at MGH, the Kleinstiver laboratory is focused on accelerating the development of CRISPR technologies. The major research goals in his laboratory are to address limitations of existing technologies, to develop new capabilities that solve outstanding needs in the genome editing field, all with the hope of transforming these technologies into genetic therapies to providing safe and effective treatments for patients.

Dr. Cafri specialized in tumor immunology and cancer immunotherapy. For the last 17 years, Dr. Cafri studies the interactions between tumors and the immune system. He began his career working on chimeric molecules to enhance vaccine activity against skin cancer at the Weizmann Institute of Science. Later on, Dr. Cafri spent 4.5 years at the National Cancer Institute (NCI) in Bethesda, Maryland, specializing in treating patients with immune cells directed against cancer mutations. During his time at the NCI, Dr. Cafri was responsible for developing two clinical trials aiming to vaccinate cancer patients with their tumor mutations. Dr. Cafri also developed a method to isolate tumor-specific immune cells from patients' blood - a technique that can bypass the need for tumor resection to develop effective cancer immunotherapies. Dr. Cafri lab develops T-cell receptor therapy for patients with common epithelial cancers and innovative genetic engineering approaches to introduce genes into human T-cells.

J Joseph Melenhorst, PhD

Professor, Pathology and Laboratory Medicine, University of Pennsylvania and Director, Biomarker Program, Parker Institute for Cancer Immunotherapy, UPenn

John Zuris, PhD

Associate Director, Editing Technologies at Editas Medicine

Karla Camacho Soto, PhD

Senior Scientist, Merck

Dr. Jan Joseph (Jos) Melenhorst Professor of Pathology & Laboratory Medicine and Director of the Biomarker Program at the University of Pennsylvania. He obtained his PhD at the University of Leiden, Netherlands (Department of Hematology) on the immune etiology of Aplastic Anemia. In 1998 he moved to the National Institutes of Health in Bethesda, Maryland, where he did his research ‐ first as a postdoc, later as a staff scientist ‐ on the immunobiology of marrow failure syndromes, leukemic disorders, and allogeneic stem cell transplantation. In 2012 he was recruited by Dr. Carl June to the University of Pennsylvania, first as Deputy Director of their clinical manufacturing (cGMP) facility. After a year he was promoted to Director of Product Development & Correlative Sciences and Adjunct Associate Professor Pathology & Laboratory Medicine. In this role, he was at the cusp of the first ever CAR T cell therapy approved by FDA: Kymriah. Further, Dr. Melenhorst led to the development of correlative assay pipeline for the first triple CRISPR/Cas9 genome edited, TCR tumor-redirected T cell product in the USA, published early January of 2020 in Science magazine. In 2020 he was promoted to full Professor at the Department of Pathology & Laboratory Medicine where he now fully focuses his effort on the translational sciences of immunogene therapies. His laboratory’s goals are to enhance our understanding and improvement of the anti-tumor efficacy and safety of adoptively transferred chimeric antigen receptor-modified T cells through correlative, mechanistic, and functional genomics approaches

John Zuris has spent the last six years at Editas Medicine, a genome editing company focused on using CRISPR to potentially cure genetic diseases. As Associate Director of Editing Technologies, he focuses on leveraging both the CRISPR-Cas12a and the CRISPR-Cas9 nuclease modalities to achieve the best editing outcome for a chosen indication. Prior to joining Editas Medicine, John completed his postdoctoral training in the laboratory of Dr. David Liu (Harvard University-Broad Institute) where he developed a lipid nanoparticle delivery system for CRISPR-Cas9 RNPs which allows for highly efficient genome editing in ex vivo and in vivo applications. This delivery technology was later utilized to successfully treat a rare form of deafness in an animal model. Before entering the CRISPR-space, John spent his graduate career elucidating the iron-sulfur cluster transfer and redox mechanisms for a metalloprotein involved in Type II diabetes under the supervision of Dr. Patricia Jennings (UC San Diego).

I received my BS in Chemistry from the University of Puerto Rico in 2009 where I synthesized and characterized the formation of supramolecular structures based on G-quadruplexes. I moved to the beautiful Arizonan desert to obtain my PhD in Chemistry from the University of Arizona under the guidance of Dr Indraneel Ghosh. During my PhD I was involved in the design and discovery of bivalent inhibitors of protein kinases using a cyclic peptide phage display approach. I also had the chance to engineer split-kinases and split-phosphatases to study signal transduction in cellular pathways. After receiving my PhD in 2015 I joined a small Biotech company where I developed mammalian cell based assays to profile kinase inhibitors promiscuity and membrane permeability. I joined Merck in 2018 as a Senior Scientist in the Protein Engineering group where I have had the chance to lead enzyme engineering programs to support manufacturing routes.

Killian S. Hanlon, PhD

Research Fellow, Harvard Medical School; Massachusetts General Hospital

Matthew Porteus, MD, PhD

Professor, Stanford University, School of Medicine

Niren Murthy, PhD

Professor, Department of Bioengineering UC Berkeley- innovative Genomics Institute

none

Matthew Porteus MD, PhD is the Sutardja Chuk Professor of Definitive and Curative Medicine and a Professor in the Department of Pediatrics, Institute of Stem Cell Biology and Regenerative Medicine and Maternal-Child Health Research Institute at Stanford. His primary research focus is on developing genome editing as an approach to cure disease, particularly those of the blood (such as sickle cell disease) but also of other organ systems as well. He received his undergraduate degree at Harvard in History and Science where his honors thesis studied the recombinant DNA controversy of the 1970s. He then completed his MD and PhD training at Stanford, clinical training in Pediatric Hematology/Oncology at Boston Children’s Hospital, and post-doctoral research training with Noble Laureate David Baltimore at CalTech. He works as an attending physician on the Pediatric Hematopoietic Stem Cell Transplant service at Lucile Packard Children’s Hospital where he cares for children under going bone marrow transplantation for both malignant and non-malignant diseases. His goal is to combine his research and clinical interests to develop innovative curative therapies. He served on the 2017 National Academy Study Committee of Human Genome Editing and currently serves on the Scientific Advisory Board for WADA on Cell and Gene Doping and the NIH NexTRAC advisory committee evaluating the emergence of new technologies.

Dr. Niren Murthy is a professor in the Department of Bioengineering at the University of California at Berkeley. Dr. Murthy’s scientific career has focused on the molecular design and synthesis of new materials for drug delivery and molecular imaging. The Murthy laboratory developed the hydrocyanines in 2009, which are now one of the most commonly used probes for imaging reactive oxygen species and commercially available from multiple sources. The Murthy laboratory has developed several new nanoparticulate technologies for drug delivery, such as the polyketals, which have been used by numerous laboratories to enhance the delivery of small molecules and proteins. The Murthy laboratory has been recently focused on developing non-viral delivery vehicles that can deliver Cas9 protein, gRNA and Donor DNA in vivo. Dr. Murthy received the NSF CAREER award in 2006, and the 2009 Society for Biomaterials Young Investigator Award.

Rama Shivakumar

Manager of Technical Applications at MaxCyte Inc.

Ramarao Vepachedu, PhD

Development Scientist IV, Leidos Biomedical Research, Inc.

Sam Sternberg, PhD

Assistant Professor, Columbia University

Rama Shivakumar is the Manager, Technical Applications at MaxCyte Inc., a clinical stage biotechnology company that specializes in a flow electroporation platform. As the company’s knowledge manager, Rama coordinates the training and data generation used by the company’s Sales, Marketing, R&D and Engineering teams to expand the adoption of MaxCyte’s technology and is responsible for developing technical notes and other customer facing materials. With over 20 years of experience in biotech, she has extensive hands on knowledge of Electroporation, Protein Production, Process Development of Viral Vector Production and Protocol Development. Rama received her graduate training in Molecular Biology from Indiana University School of Medicine at Indianapolis.

Dr. Ramarao Vepachedu is currently working as the Process Development Lead for Cell and Gene therapy projects at Leidos Biomedical Research. His areas of focus are Cell and Gene Therapy, viral vectors, viral vaccines, and monoclonal antibodies. Dr. Vepachedu earned his Ph.D. in Biochemistry from Osmania University, India in the year 1997. He conducted post-doctoral research on DNA vaccines at the Indian Institute of Science, Bangalore, India. Later Dr. Vepachedu investigated host-pathogen interactions and immune response mechanisms at Colorado State University and National Jewish Health. Dr. Vepachedu joined AstraZeneca/Medimmune in 2008 and led the process development and clinical production of live attenuated vial vaccine for the respiratory syncytial virus, recombinant proteins, and monoclonal antibodies. Dr. Vepachedu joined Leidos Biomedical at Frederick National Laboratories in 2014 and led the development of the production process for multiple CART cell therapy, AAV gene therapy, and monoclonal antibody drug products. His lab is interested in cell engineering and methods to improve cell and gene therapy drug production.

Sam H. Sternberg, PhD, runs a research laboratory at Columbia University, where he is an assistant professor in the Department of Biochemistry and Molecular Biophysics. He received his B.A. in Biochemistry from Columbia University in 2007, graduating summa cum laude, and his Ph.D. in Chemistry from the University of California, Berkeley in 2014, under the mentorship of Dr. Jennifer Doudna. He earned graduate student fellowships from the National Science Foundation and the Department of Defense, and received the Scaringe Award and the Harold Weintraub Graduate Student Award. Sam's research focuses on the mechanism of DNA targeting by RNA-guided bacterial immune systems (CRISPR-Cas) and on the development of these systems for genome engineering applications. He is the recent recipient of the NIH Director’s New Innovator Award, and is a Sloan Fellow and Pew Biomedical Scholar. In addition to publishing his work in leading scientific journals, he co-authored a popular science book with Jennifer Doudna, entitled A Crack in Creation, about the discovery, development, and applications of CRISPR gene-editing technology.

Shondra M. Pruett-Miller, PhD

Director, St. Jude Children’s Research Hospital Comprehensive Cancer Center

Ye Liu, PhD

Senior Director of Gene Transfer Technologies, REGENXBIO Inc.

Shondra Pruett-Miller, Ph.D. is an Assistant Member in the Department of Cell and Molecular Biology, the Founding Director of the Center for Advanced Genome Engineering (CAGE), and the Associate Director of Shared Resoucres for the Comprehensive Cancer Center at St. Jude Children’s Research Hospital in Memphis, TN. Shondra completed her Ph.D. in Cell and Molecular Biology from The University of Texas Southwestern Medical Center in August 2008. While at UT Southwestern, she worked in Matthew Porteus’ lab on the optimization of zinc finger nucleases for use in mammalian cells. After graduate school, she was recruited to Sigma-Aldrich as a Senior Scientist in R&D working on their CompoZr ZFN technology. In 2012, she returned to academia as the Founder and Director of the Genome Engineering and iPSC Center (GEiC) at Washington University School of Medicine in St. Louis. In 2017, she joined the Faculty at St. Jude Children’s Research Hospital where she established and is directing the Center for Advanced Genome Engineering (CAGE).

Ye Liu, PhD, is the senior director of gene transfer technologies at REGENXBIO Inc, a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Dr. Liu leads a team of multidisciplinary scientists to improve the safety, efficacy and precision of in-vivo gene therapy by developing novel AAV capsid and transgene cassette. Prior to REGENXBIO, Dr. Liu was the director of genetic engineering and vaccine development at NOVAVAX, where he developed nanoparticle vaccines against infectious diseases such as influenza and SARS-CoV. He received his PhD in biochemistry from Wayne State University and completed his postdoctoral training in genetic medicine at Johns Hopkins University with Nobel Laureate Dr. Gregg Semenza.

Agenda

Please click here to download agenda.

July 22, 2021 11:00AM - 11:10AM EDT
Introduction and Opening Remarks
July 22, 2021 11:00AM - 11:10AM EDT
Shiniu Wei
CFO & VP of Investor Relations of GenScript
July 22, 2021 11:10AM - 12:00PM EDT
Keynote Presentation
Alexander Marson, MD, PhD
July 22, 2021 11:05AM - 12:00PM EDT
Reprogramming Human T Cells with CRISPR. 
Alexander Marson, MD, PhD
Director, Gladstone-UCSF Institute of Genomic Immunology
See Abstract
Human T cells are critical effectors of immune protection from infections, autoimmune pathology, and cancer immunotherapy. We use CRISPR-mediated gene editing in primary human T cells to systematically identify genetic targets that modulate the functions of T cells in contexts ranging from immunosuppression to cancer killing. By developing and applying CRISPR based methodologies such as pooled knock-in screening, CRISPR activation, and CRISPR interference, we are pinpointing the regulatory networks controlling T cell phenotypes as well as synthetic genetic programs that can be engineered into T cells to improve their utility as cell-based therapies for disease. We are working towards a range of genetically engineered cell therapies for cancer, autoimmunity, infections and other diseases.
July 22, 2021 12:00PM - 5:00PM EDT
Track 1: Expanding CRISPR Toolbox
Ben Kleinstiver, PhD / John Zuris, PhD / Shondra M. Pruett-Miller, PhD / Sam Sternberg, PhD / Niren Murthy, PhD / Rama Shivakumar
July 22, 2021 12:00PM - 12:45PM EDT
Building More Useful CRISPR-Cas Technologies
Ben Kleinstiver, PhD
Assistant Professor, Massachusetts General Hospital and Harvard Medical School
See Abstract
  • Engineered CRISPR-Cas variants overcome natural limitations of wild-type enzymes
  • The genome is now nearly completely editable
July 22, 2021 12:45PM - 1:30PM EDT
An Engineered AsCas12a nuclease facilitates the rapid generation of therapeutic cell medicines
John Zuris, PhD
Associate Director, Editing Technologies at Editas Medicine
See Abstract
Though AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. In collaboration with Integrated DNA Technologies, we showed that this engineered variant we refer to as AsCas12a Ultra, increased editing efficiency to nearly 100% at all sites examined in HSPCs, iPSCs, T cells, and NK cells. We showed that AsCas12a Ultra maintains high on-target specificity thereby mitigating the risk for off-target editing and making it ideal for complex therapeutic genome editing applications. We achieved simultaneous targeting of three clinically relevant genes in T cells at >90% efficiency and demonstrated transgene knock-in efficiencies of up to 60%. We demonstrate site-specific knock-in of a CAR in NK cells, which afforded enhanced anti-tumor NK cell recognition, potentially enabling the next generation of allogeneic cell-based therapies in oncology. AsCas12a Ultra is an advanced CRISPR nuclease with significant advantages in basic research and in the production of gene edited cell medicines.
July 22, 2021 1:30PM - 2:15PM EDT
Operationalizing Genome Editing Across a Broad Range of Genomic and Cellular Targets.
Shondra M. Pruett-Miller, PhD
Director, St. Jude Children’s Research Hospital Comprehensive Cancer Center
See Abstract
Genome Engineering allows the easy manipulation of genomes down to the nucleotide level. CRISPR is a revolutionizing tool for generating custom edited cell and pre-clinical animal models for research. Targeted deep sequencing enables the detection and quantification of low-frequency editing events. However, the large amounts of data generated by targeted deep sequencing can be difficult to interpret and quickly analyze. We have developed a Python-based computer program called CRIS.py that allows the easy analysis of multiple types of editing events. We will show examples of how rapid deep sequence analysis has guided experimental design leading to high-efficiency genome editing in a broad range of applications. Additionally, we will discuss best practices for creating knockin cell and animal models including large insertions using long ssDNA.
July 22, 2021 2:45PM - 3:30PM EDT
Targeted DNA integration without double-strand breaks using CRISPR RNA-guided transposons
Sam Sternberg, PhD
Assistant Professor, Department of Biochemistry and Molecular Biophysics, Columbia University
See Abstract
Conventional CRISPR–Cas systems maintain genomic integrity by leveraging guide RNAs for the nuclease-dependent degradation of mobile genetic elements, including plasmids and viruses. Here we describe a remarkable inversion of this paradigm, in which bacterial transposons have coopted nuclease-deficient CRISPR–Cas systems to catalyze RNA-guided integration of mobile genetic elements into the genome. Programmable transposition requires CRISPR- and transposon-associated molecular machineries, including a novel co-complex between Cascade and the transposition protein TniQ. Donor DNA integration occurs at a fixed distance downstream of target DNA sequences, accommodates variable length genetic payloads, and functions robustly in diverse bacterial species. Deep sequencing experiments reveal highly specific, genome-wide DNA integration across dozens of unique target sites. The discovery of a fully programmable, RNA-guided transposase lays the foundation for kilobase-scale genome engineering that obviates the requirements for DNA double-strand breaks and homologous recombination.
July 22, 2021 3:30PM - 4:15PM EDT
New delivery vehicles for gene editing enzymes
Niren Murthy, PhD
Professor, Department of Bioengineering UC Berkeley- innovative Genomics Institute
July 22, 2021 4:15PM - 5:00PM EDT
Clinical Scale Gene Editing for Cell and Gene Therapy Applications
Rama Shivakumar
Manager, Technical Applications at MaxCyte Inc.
See Abstract

Genome editing technologies have enabled the precise manipulation of DNA sequences at targeted sites to achieve therapeutic effects. Engineered endonucleases like CRISPR-Cas9 institute site-specific DNA breaks to either knock out a gene or enhance the homology directed repair (HDR) based gene correction with an intact donor template. High-fidelity editing, multiplexing capacity, and the ease of implementing the CRISPR-Cas9 system have expanded the scope of programmable genetic manipulations to include simultaneous deletions or insertions of multiple DNA sequences in a single round of mutagenesis. Gene editing has many applications in basic and biomedical research, including disease modeling.

A promising cell therapy approach for hemoglobinopathies or cancer immunotherapy involves the ex vivo gene editing of autologous hematopoietic stem cells (HSCs) or T cells before administering patients.

For hemoglobinopathies, gene editing tools like CRISPR-Cas9 can be used to install a double stranded break to either knock out a gene like BCL11A or enhance the knock-in with an intact donor DNA template to correct the mutation in the beta subunit of the hemoglobin gene (HBB).

Cancer immunotherapy applications use CRISPR-Cas9 to knock out the TCR locus or checkpoint modulators to improve the efficacy and clinical outcomes of the living drug.

Here, we describe the use of a clinically validated, regulatory compliant, scalable electroporation platform for the high efficiency, low toxicity gene editing of hCD34+ hematopoietic stem cells (HSCs), T cells, and iPSC cells at a clinical scale for preclinical evaluation and commercial production of cell therapy products for Sickle Cell Disease, TCR therapy or in disease modeling.

July 22, 2021 12:00PM - 2:15PM EDT
Track 2: Genome Editing in Cell and Gene Therapy
Gal Cafri, PhD / Ramarao Vepachedu, PhD / Matthew Porteus, MD, PhD
July 22, 2021 12:00PM - 12:45PM EDT
Genetic engineering approaches to support clinical applications of  T-cell receptor libraries targeting oncogenic mutations
Gal Cafri, PhD
Immunotherapy and Genetic Engineering Group Leader, Sheba Medical Center
See Abstract
T-cells targeting shared oncogenic mutations can induce durable tumor regression in epithelial cancer patients. Such T cells can be detected in tumor-infiltrating lymphocytes and peripheral blood of patients with the common metastatic epithelial cancers. In recent years, we and others have worked toward developing libraries of T-cell receptors targeting oncogenic mutations such as KRAS and TP53. Such T-cell receptor libraries offer an opportunity to treat patients with autologous or allogeneic T-cells genetically engineered to express selected T-cell receptors. Although attractive, such clinical application of T-cell receptor libraries should be accompanied by innovative genetic engineering platforms allowing cheaper, faster, and more flexible manufacturing solutions. This talk will discuss the methods to isolate, clone, and validate T-cell receptors targeting oncogenic mutations, the therapeutic potential of such libraries, and the genetic engineering platforms currently used for clinical manufacturing. We will also address the genetic engineering tools needed to allow such an approach to become widely and commercially applicable.
July 22, 2021 12:45PM - 1:30PM EDT
CRISPR/Cas9-based genome editing for autologous CAR-T cell production
Ramarao Vepachedu, PhD
Development Scientist IV, Leidos Biomedical Research, Inc. 
See Abstract
Gene editing technologies such as CRISPR/Cas9 have greater flexibility and high efficiency. CRISPR technology enables targeted insertion of transgenes at the desired locus and has the ability to multiplex knocking out of multiple genes. These features provide a great opportunity to use this technology to develop next-generation CAR T cells. The popular method for the generation of CART cell drug product is delivery of CAR and its integration into the T cell genome using viral vectors. Lentivirus or gamma retrovirus-based CAR delivery was used in multiple CART cell productions. CART cell production using viral vectors to deliver the transgene results in the random insertion of CAR sequence across the whole genome. In addition to random CAR insertion viral vectors also deliver partial viral sequences into the cell genome. These things together could disrupt essential gene functions and affect surrounding functional gene expression. CRISPR/Cas9 gene-editing technology can achieve targeted insertion of CAR construct sequence in the desired locus such as T cell receptor locus (TRAC) or any genomic safe harbor sites. The transition from viral vectors to CRISPR/Cas9 based gene editing requires multiple reagents that are GMP compatible. A lot of progress was achieved in the commercial availability of CRISPR/Cas9 reagents in recent years for the generation of cGMP CART drug products. However, there are multiple issues that require careful attention in process development to achieve a reliable cGMP process for CRISPR/Cas9 based cell therapy drug product. These include gene knockout and knock-in efficiency, off target and on target effects, and the ability to achieve the desired quantity of the drug product. A study on the feasibility of using CRISPR/cas9 gene-editing technology for autologous CART drug production and the relevance of this technology for the generation of safe drugs for the patients will be discussed.
July 22, 2021 1:30PM - 2:15PM EDT
Targeted Integration in Stem Cells
Matthew Porteus, MD, PhD
Professor, School of Medicine, Stanford University
See Abstract
We have harnessed homologous recombination to modify the genome of human stem cells with high frequencies (>40%). By designing the recombination donor in different ways, we can achieve a wide range of targeted integration outcomes including creating single nucleotide changes, inserting one gene into another gene, simultaneously inserting two genes into the genome, or even replacing one gene with another. In this talk, I will discuss some of these applications to engineering human stem cells to treat patients.
July 22, 2021 2:45PM - 5:00PM EDT
Track 3: Enzyme and AAV Engineering
Killian S. Hanlon, PhD / Karla Camacho Soto, PhD / Ye Liu, PhD
July 22, 2021 2:45PM - 3:30PM EDT
Library-selected AAV variants can effectively translate to non-human primates in the spinal cord and cochlea
Killian S. Hanlon, PhD
Research Fellow, Harvard Medical School, Massachusetts General Hospital
See Abstract

AAV peptide display libraries allow for the generation of novel variants capable of high-level transduction. We previously described an AAV peptide display library combined with a sensitive transduction reporter, iTransduce, that enabled the discovery of potent capsids in the mouse brain after only two rounds of selection via intravenous injection. Analogous to drug repurposing, AAV capsids can be used for gene delivery applications other than originally intended. With that in mind, we tested two of the capsids, AAV-F and AAV-S, from our selection in mice to transduce non-human primate (NHP) spinal cord and cochlea, respectively.

We found that intrathecally injected AAV-F mediated higher expression in motor neurons and interneurons compared to AAV9 in the thoracic and lumbar regions, despite lower numbers of genomes per cell in AAV-F-treated animals. AAV-S was tested in the inner ears of mice and cynomolgus macaques, and in both cases drove robust, high-level transduction throughout the cochlea. Further, AAV-S was able to rescue the deafness phenotype of a mouse model of Clarin-1 related Usher Syndrome. Overall, this work serves to highlight that AAV variants selected from our library system can translate effectively to clinically relevant large animals, and provides further evidence for the benefits of capsid repurposing.

July 22, 2021 3:30PM - 4:15PM EDT
Improved chemistry by combining enzyme engineering, enzyme immobilization, and flow chemistry
Karla Camacho Soto, PhD
Senior Scientist, Merck
See Abstract
Biocatalysis, protein engineering, and flow chemistry are key enabling technologies that can yield drastically shorter and greener chemical processes. We sought to leverage these technologies to realize an improved synthesis. A cheap and green chemical commodity was identified as a starting material that allowed the generation of a key intermediate in the synthesis in a stepwise reaction. As an initial proof of concept, an enzyme-catalyzed reaction was demonstrated with modest yields and selectivity. However, the initial enzyme and process would not be sufficient to support large scale synthesis. To improve the synthesis, we engaged in enzyme evolution, enzyme immobilization, and flow chemistry. Through several rounds of evolution the enzyme was evolved to reach high conversion, selectivity and stability in the presence of organic solvents.
July 22, 2021 4:15PM - 5:00PM EDT
Discovering the Next Generation AAV Vector Through Capsid Engineering and Expression Cassette Optimization
Ye Liu, PhD
Senior Director of Gene Transfer Technologies, REGENXBIO Inc.
July 22, 2021 5:00PM - 5:45PM EDT
Closing Keynote Presentation
J Joseph Melenhorst, PhD
July 22, 2021 5:00PM - 5:45PM EDT
Response to Second Generation CAR T Cell Therapy: It Takes (at least) Two to Tango
J Joseph Melenhorst, PhD
Professor, Pathology and Laboratory Medicine, University of Pennsylvania and Director, Biomarker Program, Parker Institute for Cancer Immunotherapy, UPenn
See Abstract
Though tumor targeting using chimeric receptors (CAR) engineered to bind tumor-associated surface proteins such as CD19 in B cells have demonstrated remarkable efficacy in cancer, this therapy has hit a glass ceiling w.r.t. initial and durable remissions. Inclusion of a costimulatory domain in the CAR design have solved much of limited clinical efficacy issues, some challenges remained. We have recently demonstrated that T cell-intrinsic mechanisms solved part of the glass ceiling conundrum in leukemia, we recently demonstrated that primary chronic lymphocytic leukemia cells elicit a blunted response of second generation CAR T cells, even when using normal donor CAR-engineered T cells. In my talk I will highlight our discoveries in T cell- and tumor-intrinsic determinants of anti-CD19 CAR T cell responses in this disease.
July 22, 2021 5:45PM - 6:00PM EDT
Closing Remarks
July 22, 2021 5:45PM - 6:00PM EDT
Ray (Rui) Chen, PhD
President of Life Science Group of GenScript
Organizer
Target Audience
✔ Protein Engineering Researchers

✔ Immunotherapy Researchers

✔ Gene and Cell Therapy Scientists

✔ Vaccine Development Scientists

✔ Biotechnologists

✔ Business Entrepreneurs

Powerd by The GenScript Gene & Cell Engineering Virtual Summit.