ISSUE NO. 37 — Quantitative PCR (qPCR) and Droplet Digital (ddPCR): Leading-Edge Analysis for Your Gene Therapy Programs
The gene therapy landscape continues to accelerate in preclinical and clinical research, with programs constantly in development for targeted, personalized medicines. The goal is to safely incorporate genetic alterations to restore and repair the proteins of missing and/or faulty genes. Gene therapy requires DNA and/or RNA delivery and analysis, and while most ongoing research involves therapies being delivered in vivo via adeno-associated viral (AAV) vectors, other in vivo delivery methods are on the rise.
Quantitative, digital, and reverse transcription polymerase chain reactions (qPCR, dPCR, and RT-PCR, respectively) are fast and cost-effective techniques employed by Altasciences. These methods are invaluable for quantitative analysis of gene expression and for analyzing genetic variation in amplified DNA and RNA. This ability to analyze variation from limited samples has made genetic diagnosis easier than ever. But how are PCR analysis techniques applied? And how are they incorporated into studies?
Issue 37 of The Altascientist takes a closer look at these techniques, with in-depth information on:
- qPCR, dPCR, and RT-PCR and their utilities—including droplet digital PCR (ddPCR);
- regulatory considerations;
- PCR applications, advantages, and comparisons; and
- case studies.
HOW DOES PCR WORK?
PCR is a laboratory technique for rapidly amplifying millions of copies of specific DNA segments to be studied in greater detail. The process utilizes short synthetic DNA fragments called primers to choose a section of the genome to be amplified. Multiple rounds of DNA synthesis will then take place to amplify that section. This process is done using thermal cycling of a reagent cocktail. Reactions contain buffers to ease the DNA polymerase enzymatic amplification of nucleic acids, and target-specific primers and probes. Primers and fluorescent probes are designed and optimized for each assay and platform, to determine the appropriate region or target for amplification.
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ISSUE NO. 36 — Nonclinical Studies in Cell and Gene Therapy
Recent advances in gene therapy have allowed us to approach diseases differently than medicines and surgery—they are “living drugs” that provide cures for a number of conditions by terminating the disease process at the cellular or genetic level. It is estimated that there are over 6,000 monogenic diseases, affecting over 350 million people worldwide; for these diseases, cell and gene therapy may provide hope for a cure.
However, there are significant challenges associated with the successful development of these complex, leading-edge therapies. The in vivo nonclinical study of cell and gene therapies includes a thorough understanding of on-and-off-target activity, immune responses, and other adverse events just to name a few. All of which require careful monitoring, and rigorous assessments.
In Issue 36 of The Altascientist, we take a deep dive into the essential factors in the development of nonclinical cell and gene therapy—including insights into mitigating complex challenges and maximizing translational opportunities to first-in-human trials.
This comprehensive publication covers the following:
- ICH S-12 guideline on biodistribution studies
- species selection
- choosing the right vector for your cell and gene therapy studies
- the importance of germline mitigation
- exaggerated on-target effects
- immunogenicity
- nonclinical study planning
- case studies from Altasciences
GENE THERAPY VS. CELL THERAPY: WHAT IS THE DIFFERENCE?
Gene and cell therapies are often discussed together, but they are not always interchangeable. Some therapies are considered both cell and gene therapies, as they alter genes in specific types of cells.
Gene therapy involves introducing or substituting a faulty gene. There are three primary vectors employed in gene therapy: adeno-associated virus (AAV), adenovirus, or lentivirus vectors.
Cell therapy on the other hand, involves the injection of living cells (either autologous or allogeneic) into a subject. This encompasses immunotherapy, oncology, and regenerative medicine. Examples of cell therapies include CAR-T and natural killer (NK) cell therapies.
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The Nonhuman Primate Model of CNS Therapies and Utility of Adeno-Associated Viral (AAV) Vectors in Gene Therapy: From Discovery to IND-Enabling Studies
Altasciences Chosen by Virpax to Support the Development of a New Drug to Prevent Spread of Flu-like Viruses
Laval, Québec, September 21, 2023 - Altasciences is pleased to have been chosen by Virpax Pharmaceuticals, Inc. (NASDAQ:VRPX) (“Virpax”), a company specializing in developing non-addictive products for pain management, PTSD, central nervous system (CNS) disorders, and viral barrier indications, to conduct preclinical studies in support of their development of quaternary ammonium palmitoyl glycol chitosan (GCPQ, under the trade name of AnQlar™). AnQlar is a nanoparticle intended to help prevent the spread of negatively charged viruses such as COVID-19 and influenza via intranasal spray, and has been shown to inhibit the ability of the virus to replicate at non-toxic concentrations.
In development since 2022, the project has so far seen the completion of safety assessment utilizing intranasal administration at Altasciences’ preclinical site in Columbia, MO. A cardiovascular study was also completed at Altasciences’ preclinical facility in Scranton, PA.
Bioanalytical sample analysis for the GLP studies is currently ongoing. “We are very pleased to be working with Virpax again and are satisfied with the trajectory our studies have taken. The final step for this program will be a bioanalytical sample analysis. Once samples are validated, this will conclude the IND package” said Kyle Klepner, Senior Scientist, Study Director, Safety Assessment, at Altasciences.
Steve Mason, Co-Chief Operating Officer, Altasciences, added: “The creation of AnQlar as a treatment, if successful, could be a huge leap forward in preventing the spread of influenza and similar viruses. We look forward to further collaboration with Virpax in the near-future.”
Sheila Mathias PhD, Chief Scientific Officer, Virpax, also said of the project: “Our work with Altasciences over the last year has been both exceedingly productive and rewarding demonstrating tangible results, and the preclinical support provided has been vital in ensuring the progress of this project."
About Altasciences
Altasciences is an integrated drug development solution company offering pharmaceutical and biotechnology companies a proven, flexible approach to preclinical and clinical pharmacology studies, including formulation, manufacturing, and analytical services. For over 25 years, Altasciences has been partnering with sponsors to help support educated, faster, and more complete early drug development decisions. Altasciences’ integrated, full-service solutions include preclinical safety testing, clinical pharmacology and proof of concept, bioanalysis, program management, medical writing, biostatistics, clinical monitoring, and data management, all customizable to specific sponsor requirements. Altasciences helps sponsors get better drugs to the people who need them, faster. To learn more about Altasciences, visit altasciences.com.
About Virpax
Virpax is developing branded, non-addictive pain management product candidates using its proprietary technologies to optimize and target drug delivery. Virpax is initially seeking FDA approval for two prescription drug candidates that employ two different patented drug delivery platforms. Probudur™, a single injection liposomal bupivacaine formulation being developed to manage post-operative pain, and Envelta™, an intranasal molecular envelope enkephalin formulation being developed to manage acute and chronic pain, including pain associated with cancer.
Virpax is also using its intranasal molecular envelope technology (MET) to develop two other product candidates. PES200, is a product candidate being developed to manage PTSD, and NobrXiol™, a product candidate being developed for the nasal delivery of a pharmaceutical-grade cannabidiol (CBD), for the management of rare pediatric epilepsy.
Having recently acquired global rights to NobrXiol, Virpax has competitive cooperative research and development agreements (CRADAs) for all three of its prescription drug candidates, two with the National Institutes of Health (NIH) and one with the Department of Defense (DOD).
Virpax is currently seeking approval of two nonprescription product candidates: AnQlar, which is being developed to inhibit viral replication caused by influenza or SARS-CoV-2, and Epoladerm™, a topical diclofenac spray film formulation being developed to manage pain associated with osteoarthritis.
For more information, please visit virpaxpharma.com or follow on Twitter, LinkedIn, and YouTube.
Virpax Media Contact:
Robert Cavosi
RooneyPartners
+1 646 638-9891
rcavosi@rooneypartners.com
Julie-Ann Cabana
Altasciences
+1 514 601-9763
jcabana@altasciences.com
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