Gene therapy involves introducing a functional gene into the patient's cells to replace a missing or defective one. It has revolutionized the field of medicine and has the potential to cure a wide variety of genetic disorders. 

The two main technologies used for gene therapy are viral-based and non-viral gene editing. 

The primary advantage of viral-based gene editing is that viruses are highly efficient at transferring genes into cells. However, there are risks associated with viral-based gene therapy, such as the potential for the virus to cause immune system reactions or to integrate into the patient's DNA in harmful ways.

Non-viral gene editing, such as CRISPR, has emerged as a promising alternative to viral-based gene therapy. CRISPR is a revolutionary gene-editing technology that allows scientists to modify genes with unprecedented precision and ease. Non-viral gene editing has several advantages over viral-based gene therapy, including a lower risk of immune system reactions and less potential for the genetic material to integrate into the patient's DNA.

The quality of the reagents used for development of therapies is critical for the success. Regardless of the type of gene therapy you are developing, GenScript has an extensive solution of high-quality services and products that can fulfill you development needs. 

In this webinar, we will discuss GenScript solutions for discovery, lead generation and optimization, and pre-clinical and clinical development of gene therapies.

Learning Objectives:

• Learn about the methodologies available for in-vivo gene editing 
• Learn about the critical steps for each technology and how to best optimize
• Discover the complete toolbox of technologies available from GenScript

T cell lymphocytes play a central role in the adaptive immune response. They are an essential tool of adoptive cell therapy for the treatment of chronic viral infections and malignant diseases. However, the development of cell-based therapy products generally requires the production of a large quantity of high-quality viable T cells in a controlled environment. Stirred-tank bioreactors can offer a suitable environment for the culture of T cells by providing homogeneous distribution of nutrients and gases, along with the maintenance of cells and molecules in suspension with a high process control capability.

Learning Objectives:

• Extend your knowledge on the possibilities of stirred-tank bioreactor-based T cell culture process development.

• Identify the potential and challenges associated with T cell culture.

• Understand how stirred-tank bioreactors can help addressing these challenges

Cell and gene therapy is at the forefront of medical innovation, offering transformative potential for treating complex diseases. However, achieving success in these therapies requires meticulous attention to the quality of gene editing components and regulatory compliance. This webinar will explore how quality and regulatory standards for gene editing reagents influence the development and application of these technologies, as well as the FDA's Cell and Gene Therapy Guidance.

Participants will gain insights into the key distinctions between gene editing component grades and their implications for development. We will discuss how a consistent platform can streamline the transition from preclinical stages to clinical trials. Through real-world case studies, we will address common challenges in cell and gene therapy (CGT) development and present effective strategies for overcoming them. Additionally, selecting phase-appropriate components can enhance clinical outcomes while effectively managing costs. Finally, the webinar will highlight how GenScript’s expertise and support contribute to achieving successful Investigational New Drug (IND) submissions and compliance with FDA regulations.

Key Takeaways:

• Gene Editing Component Grades: Differences and impact on development.

• Platform Consistency: Streamlining transitions from preclinical to clinical trials.

• Case Studies: Strategies to overcome common CGT challenges.

• Phase-Appropriate Components: Enhancing outcomes and managing costs.

• GenScript’s Role: Support for successful IND submissions and FDA compliance.

Learning Objectives:

• Understand the Impact of Gene Editing Component Grades
• Ensure Regulatory Compliance with FDA Guidelines
• Gain Insights into cGMP Manufacturing Expertise and Capacity

The use of biologic-based therapeutics has revolutionized our ability to treat complex diseases such as cancer- and autoimmune-related disorders. Biologic-based therapeutics are known to generate anti-drug immune responses or immunogenicity in clinical patients which can lead to altered pharmacokinetics, decreased drug efficacy, and unwanted adverse clinical events. Assays designed to detect and assess anti-drug immune responses are used to help monitor patients and improve drug safety. Utilizing a tiered approach, screening assays are developed first to identify patients that are potentially positive for anti-drug-specific antibodies. Patients that screen positive are subjected to additional tiers of testing that include a confirmation assay to confirm the presence of expected anti-drugspecific antibodies, a titer assay to assess relative levels of anti-drug-specific antibodies, and, depending on the drug’s mechanism of action or concerns of adverse clinical reactions, further characterization such as drug neutralization and anti-drug antibody isotyping. This tiered approach can prove to be detrimental to clinical samples from exposure to multiple cycles of testing, freeze thaws, and repeated handling by lab personnel. Multiplexing some of these assays together may streamline the characterization of anti-drug immune responses and help reduce the repeated usage of clinical samples. In this study, we combined a screening assay and anti-drug isotyping assays into one multiplexed assay using the Luminex® xMAP® Technology. The multiplexed assay was developed and validated to meet the FDA recommended guidelines for immunogenicity assessments. These results show that multiplexed assays perform comparably to industry standards. This study should encourage labs to explore the use of multiplexing immunogenicity assays to characterize anti-drug antibody responses quickly, with less repeat testing and reduced sample handling.

Learning Objectives:

• Identify the impact of anti-drug immune responses on biologic-based therapeutics, including their effects on pharmacokinetics, drug efficacy, and clinical outcomes.
• Describe the tiered approach used in immunogenicity testing, including screening assays, confirmation assays, titer assessments, and additional characterization techniques.
• Explain the benefits of multiplexed assays in immunogenicity testing, particularly in reducing sample handling and streamlining the characterization of anti-drug antibodies.

Join this year's poster presenters in the Poster Hall during the Poster Discussion, Wednesday, October 16th, from 10:00am – 11:00am PDT, to chat live about their posters and latest research and findings.

In today’s diagnostic test development landscape, the path to commercialization and generating topline revenue is marked by peaks and valleys. One of the first hurdles is navigating the complex regulatory environment and the oversight of in-vitro diagnostics (IVD) when labeled as a laboratory developed test (LDT). Dynamic changes to meet validation requirements prior to commercialization requires design control—a concept formally recognized within the FDA regulatory framework. Even when meeting these validation requirements, there is a long and arduous road to attain revenue and become profitable. Many companies initially adopt a cash-pay model at the time of commercial launch, but achieving market saturation and securing contracts with medical payers for “in-network” reimbursement are critical for long-term viability. This process must begin as early as the ideation phase by demonstrating the clinical return on investment (ROI) and illustrating how the test will impact clinical management and reduce the healthcare burden. In this talk, we will explore best practices for achieving successful market penetration of clinical diagnostic tests, from R&D ideation to commercialization.

Learning Objectives:

• Discuss the requirements behind validating a clinical diagnostic test
• Review the pathway of clinical diagnostic test development from ideation to commercialization
• Analyze the clinical ROI needed in obtaining in-network contracts and long-term viability 

Across the entire spectrum of the life sciences sector, from academia and hospitals to pharmaceutical and biotech companies, enormous amounts of resources are invested in the development of new treatments to combat the largest public health challenges. This ranges from advanced cancer treatments that significantly improve survival, to treating previously untreatable diseases through gene therapy. The absolute breakthrough in nanomedicine technology was recently signified with over 70% of the global population having now received a COVID-19 vaccination, many of which were mRNA vaccines. However, the technologies available to analyse these new medicines continue to lag behind. There remains a largely unmet need for specifically designed analytical tools that are more sensitive and capable of accelerating R&D and improving quality control of nanoformulations. This presentation will guide you through a range of novel analytical approaches, their capabilities, goals and limitations to improve translation and efficacy of these novel therapies.

Learning Objectives:

• Review what kinds of nanoformulations and non-viral modalities are available and in development and their key characteristics
• Discuss the key analytical challenges in the development and translation of these new modalities
• Describe the core concepts of novel analytical techniques addressing these analytical challenges 

Gene therapy is defined as the treatment of disease by transfer of genetic material into cells, to prevent, treat and potentially even cure a disease. Gene therapies can work by several mechanisms: 1) replacing a disease-causing gene with a healthy copy of the gene; 2) inactivating a disease-causing gene that is not functioning properly; 3) introducing a new or modified gene into the body to help treat a disease. There are a variety of types of gene therapy platforms. This presentation will explore the viral vectors available for gene transfer as well as their advantages and disadvantages. Viruses have evolved a natural ability to deliver genetic material into cells and are currently the most commonly used gene therapy platforms. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells. There are three universal requirements for viral gene therapy vectors. First, the delivery system must be safe and immunologically inert. Second, it must protect the genetic material from degradation. Third, the vector must encode an effective therapeutic gene that has sustained expression at a defined target site. Here we will take a deeper look at the advancement achieved over the past 30 years in developing, engineering, and production of highly defective, non-toxic herpes simplex virus (HSV) vectors platforms. We will discuss mechanisms of genetic regulation through cell-specific and inducible promoters, which allow to express gene products only in specific cells and to control their transcriptional activation. We will explore how noncoding DNA regions, such as insulator - small DNA elements that overcome the host’s epigenetic silencing of foreign DNA- are essential in preserving stable transgene expression in vivo. By the end of this presentation the participant would be able to 1) discuss the advantages and disadvantages of gene therapy vector-based platforms; 2) explain HSV-based gene therapy platforms and 3) describe how epigenetic changes play a pivotal role in maintaining transgene expression.

Learning Objectives:

• Discuss the advantages and disadvantages of gene therapy vector based platforms
• Explain HSV-based gene therapy platforms
• Describe how epigenetic changes play a pivotal role in maintaining transgene expression

A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient transduction of airway epithelial cells to achieve therapeutic correction. Vehicles such as lysophosphatidylcholine (LPC), EGTA, perfluorocarbon, or methylcellulose have been used to enhance gene transfer of Ad, AAV or lentiviral vectors. However, advancing these formulations to a clinical setting adds an additional layer to translating a gene therapy therapeutic. To this note, we screened FDA approved reagents for their ability to enhance viral vector transduction of primary human airway epithelial cells and identified hypertonic saline as a candidate that conferred a clear benefit. Hypertonic saline (3-7%) is frequently administered as an agent to enhance mucociliary clearance in people with CF. Hypertonic saline transiently disrupts epithelial cell tight junctions, but its ability to improve gene transfer has not been investigated. Here we asked if increasing NaCl tonicity in the vector formulation enhances the transduction efficiency of 3 gene therapy vectors: adenovirus, AAV, and lentiviral vectors. We observed that vectors formulated in vitro with 3-5% NaCl exhibited markedly increased transduction for all 3 platforms, leading to phenotypic correction of the anion channel defect in primary cultures of human CF epithelial cells. The NaCl-enhanced transduction was enhanced by ionic strength but not osmolarity, or pH. Focused Ad entry studies suggest viral entry remains receptor dependent and requires low pH endosomal escape. Gene transfer in vivo was also enhanced in mouse and pig airways by formulating vectors in NaCl (5% or 7%). Increasing saline tonicity has the potential to increase the viral delivery efficacy with a reduced amount of vector. These studies open the door to many possibilities for other genetic lung diseases, far beyond CF.

Learning Objectives:

• Identify the effects of hypertonic saline on transduction efficiency for adenovirus, AAV, and lentiviral vectors in airway epithelial cells.
• Differentiate the impact of ionic strength versus osmolarity and pH on NaCl-enhanced gene transfer.
• Evaluate the potential of hypertonic saline formulations to improve gene therapy outcomes in cystic fibrosis and other genetic lung diseases.

Inborn errors of metabolism (IEMs) are rare, devastating disorders caused by pathogenic variants in genes encoding key metabolic enzymes, with the liver playing a critical role in over 140 IEMs. Liver transplantation is a treatment option but is limited by donor shortages and lifelong risks. To address this unmet need, we aim to develop a master protocol for personalized base-editing and prime-editing therapies for severe, rare hepatic IEMs.

We focused initially on phenylketonuria (PKU), an IEM resulting from variants in the phenylalanine hydroxylase (PAH) gene. Building on prior work with in vivo base-editing and prime-editing solutions for the common PAH variants R408W and P281L, we extended our research to other frequent PKU variants. Using a novel platform where collinear genomic segments with patient-specific variants were introduced into HuH-7 hepatocytes, we rapidly screened and identified base-editing solutions for the PAH c.1066–11G>A, R261Q, and R243Q variants. These solutions showed comparable or better efficacy in vitro and were validated in vivo in humanized mouse models, with off-target risks minimized.

Simultaneously, we applied this workflow to pathogenic variants from other liver-centered diseases such as galactosemia, citrullinemia type 1, argininosuccinic acidemia, methylmalonic acidemia, and pseudoxanthoma elasticum. Editing solutions were identified and validated in humanized mouse models. To accelerate testing, we are using multi-humanized mice with human variants inserted into the Rosa26 locus. Our goal is to establish a platform regulatory framework, where IND-enabling studies for a "leader" hepatic IEM therapy expedite “follower” IND amendments, facilitating personalized corrective editing therapies for patients within months.

Learning Objectives:

• Identify the role of base editing and prime editing in correcting genetic variants associated with phenylketonuria (PKU).
• Differentiate the efficacy of base-editing solutions for various PKU variants, including R408W, P281L, c.1066–11G>A, R261Q, and R243Q.
• Evaluate the application of editing technologies in treating additional liver-centered inborn errors of metabolism.

The development of cell and gene therapies faces immense pressure in terms of time and cost. Advanced therapy medicinal products (ATMPs) demand stringent quality control measures to ensure safety and efficacy. Nucleic acid extraction is a critical initial step in viral vector quality control and essential for assessing transfection efficiency and for verifying transgene expression or viral DNA integration. In this session, we will explore the advantages and limitations of various nucleic acid extraction techniques, focusing on how to streamline development timelines, reduce costs, and maintain high-quality outcomes.

Learning Objectives:

• Discuss the key challenges in RNA/DNA extraction
• Evaluate different extraction techniques and their impact
• Design strategies to optimize project timelines, reduce costs, and ensure high-quality results

The path from research discovery to effective immune cell therapies requires innovative approaches to match the challenges we face. Examining the full richness of biological complexity—moving from incremental snapshots to a complete systems view—can uncover molecular insights into therapeutic efficacy and toxicity, and accelerate the development of novel treatments. Access the resolution you need to explore complex tumor heterogeneity, suppressive tumor microenvironments, poor trafficking, and intrinsic T-cell dysfunction with single cell and spatial multiomics. Identify novel cell types and biomarkers, track clonal behavior, and monitor the behavior of cells over time. Join us to learn how Chromium Single Cell and Visium Spatial solutions from 10x Genomics can transform the way you approach cancer biology and tackle immune cell therapies from a bold new vantage point. 

Learning Objectives:

• Review 10x Genomics’ portfolio overview
• Define how 10x’s solutions have been used in the field
• Identify advantages of single cell and spatial genomics approaches