Demystify Your Disease’s R&D Readiness

Genetic Therapies

Gene therapy, genome editing, RNA-based therapy, and cell therapy are several of the promising therapies making headlines in the popular press. These advanced biologic products have the potential to treat, and in some cases cure, many types of rare diseases and cancer. However, it can be hard to know if any have the possibility to treat your disease. You may wish to gain a basic understanding of these intriguing advances and then discuss their relevance to your disease with your Medical/Scientific Advisory Board and possibly experts in the respective therapy field.

Gene therapy is a technique that modifies a person’s genetic material (DNA or RNA) to treat or cure a disease.
- Gene therapy can replace, correct, or inactivate a disease-causing gene. It can introduce a new or modified gene. Gene therapy may also target RNA transcripts or messenger RNA (mRNA).
- The FDA definition of gene therapy includes gene replacement therapy (such as adeno-associated virus gene therapy), genome editing (such as CRISPR-Cas9), RNA-based therapies (such as small interfering ribonucleic acid and antisense oligonucleotide), and cell-based gene therapy (such as CAR T-Cells) when these techniques are used in humans.
- Gene therapy is being studied to treat diseases including cancer, genetic diseases, and infectious diseases.
- Learn more about gene therapy:
  - FDA: What is Gene Therapy? Is a short webpage defining key terms used by medical researchers.
  - FDA: Human Gene Therapy for Rare Diseases is a guidance document providing recommendations to sponsors developing human gene therapy products intended to treat a rare disease in adult and/or pediatric patients. The guidance includes recommendations regarding the manufacturing, preclinical, and clinical trial design issues for all phases of the clinical development program.
  - Global Genes offers video recording of sessions with expert panelists and a written web-based guide to gene therapy:
    - Global Genes LIVE!: Is Gene Therapy Right for Your Disease? (2020) is a 1 hour video recording of a session offered during their 2020 virtual Summit.
      - Reviews recent developments in gene therapy technologies.
      - Outlines what conditions and mutations are the best fit for these solutions
    - Global Genes LIVE!: Gene to Therapy: How Individualized Therapies Are Becoming Reality (2020) is also a 1 hour video recording of a session offered during their 2020 virtual Summit.
      - Shares case studies of the progress enabled by personalized medicine.
      - Discusses the risks and opportunities new technologies have created in this space as well as the hope personalized medicine brings for the future of rare disease.
    - Global Genes LIVE!: Harnessing the Power of New Genomic Frontiers (2020) is also a 1 hour video recording of a session offered during their 2020 virtual Summit.
      - Shares inspiring stories of leveraging new science to understand and treat rare diseases.
    - Global Genes RareToolkits: A Guide to Gene Therapy (2018) is a comprehensive introduction web-based guide to gene therapy.
      - Describes the basics of gene therapy, current challenges and future pursuits.
      - Provides links to more videos and other information resources at the end of the guide.
  - The National Organization for Rare Disorders (NORD) offers 5 RareEDU Webinars from 2019 to 2020 focused on gene therapy:
CRISPR-Cas gene editing system (CRIPSR) is just one type of genome editing, but is currently regarded as an editing technique that may be able to be treat or cure human genetic disorders.
- CRISPR-Cas gene editing system is composed of a short strand of RNA, often called guide RNA (gRNA), that is made to target a specific sequence of DNA. The gRNA strand is surrounded by short repeated sequences of RNA that act as scaffolding. The system is linked to an enzyme that is capable of cutting double-stranded DNA.
- Currently CRISPR is most commonly used to make disease cell and animal models, but is also being explored as to perform rapid diagnosis and to correct disease causing genetic changes.
- There are different CRISPR-Cas gene editing systems, including CRISPR-Cas9.
- CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.
- Cas stands for CRISPR associated protein.
- Learn more about genome editing and CRISPR-Cas9:
  - What is Genome Editing? is a short webpage by the the National Human Genome Research Institute (NHGRI) introducing CRISPR and also provides links to more in depth CRISPR topics at the bottom of the page.
  - What are genome editing and CRISPR-Cas9? is a short webpage by MedlinePlus (from the National Library of Medicine) introduces genome editing in plain language and also provides links to other resources including published scientific journal articles focused on the topics.
  - What is CRISPR-Cas9? is a webpage by Wellcome Genome Campus YourGenome that provides basic information about CRISPR-Cas9 in easy to read bullet points and includes diagrams depicting the steps of genome editing.
Chimeric Antigen Receptor T-Cells (CAR T-Cells) is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells.
- CAR T-Cells are made by adding a gene for a special receptor that binds to a certain protein on the patient’s cancer cells to the patient’s T cells harvested from their own blood. The special receptor is called a chimeric antigen receptor (CAR).
- Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion, enabling the a patient’s immune cells to fight their own cancer.
- CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers is a webpage by the National Cancer Institute that provides an overview of the development of the CAR T-cell therapy as well as its expanding its use.

Resources

Disease Knowledge

The 10 Things You Need to Pursue Research For Your Disease: What Are the Options for Research and Why is it so Hard? Global Genes (link)

Research Tools

How Biomarkers Can Improve the Drug Development Process U. S. Food and Drug Administration (FDA) (link)

Rare Diseases Registry Program (RaDaR) National Center for Advancing Translational Sciences (NCATS) (link)

Genetic Therapies

What is Gene Therapy? U. S. Food and Drug Administration (FDA) (link)

Human Gene Therapy for Rare Diseases U. S. Food and Drug Administration (FDA) (link)

Global Genes LIVE!: Is Gene Therapy Right for Your Disease? Global Genes (link)

Global Genes LIVE!: Gene to Therapy: How Individualized Therapies Are Becoming Reality Global Genes (link)

Global Genes LIVE!: Harnessing the Power of New Genomic Frontiers Global Genes (link)

A Guide to Gene Therapy Global Genes (link)

Gene Therapy Yesterday, Today and Tomorrow National Organization for Rare Disorders (NORD) (link)

The Science Behind Gene Therapy National Organization for Rare Disorders (NORD) (link)

The FDA's Role in Gene Therapy National Organization for Rare Disorders (NORD) (link)

Understanding the Gene Therapy Process and Aftercare National Organization for Rare Disorders (NORD) (link)

Life After Gene Therapy National Organization for Rare Disorders (NORD) (link)

What is genome editing? National Human Genome Research Institute (NHGRI) (link)

What are genome editing and CRISPR-Cas9? MedlinePlus (link)

What is CRISPR-Cas9? Wellcome Genome Campus YourGenome (link)

Somatic Cell Genome Editing National Center for Advancing Translational Sciences (NCATS) (link)

CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers National Cancer Institute (NCI) (link)

Finding Disease and Technology Info

PubMed National Library of Medicine (NLM) (link)

Creating Alerts: PubMed NIH Library (link)

ClinicalTrials.gov National Library of Medicine (NLM) (link)

CenterWatch Clinical Trial Listings CenterWatch (link)

Institutional Review Boards Frequently Asked Questions U.S. Food and Drug Administration (FDA) (link)

Research Portfolio Online Reporting Tool (RePORTER) National Institutes of Health (NIH) (link)

List of Registries National Institutes of Health Clinical Center (link)

Keeping Up with Advances

Free NIH Email Updates National Institutes of Health (NIH) (link)

News & Events for Human Drugs U. S. Food and Drug Administration (FDA) (link)

What's New Related to Drugs (CDER New) and other drug-related topics U. S. Food and Drug Administration (FDA) (link)

Preclinical Innovation National Center for Advancing Translational Sciences (NCATS) (link)

Core Technologies National Center for Advancing Translational Sciences (NCATS) (link)

Monthly NCATS e-newsletter National Center for Advancing Translational Sciences (NCATS) (link)

Receive NCATS Announcements National Center for Advancing Translational Sciences (NCATS) (link)

Accomplishments in Genomic Medicine National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG) (link)

2019 Genomic Medicine Year in Review National Human Genome Research Institute (NHGRI) Genomic Medicine Working Group (GMWG) (link)

News and Events from NCI-funded Research and Programs National Cancer Institute (NCI) (link)

Genomics and Precision Health Weekly Update Centers for Disease Control and Prevention (CDC) (link)

PhRMA: Scientific Discoveries Pharmaceutical Research and Manufacturers of America (PhRMA) (link)

PhRMA: Research and Development Pharmaceutical Research and Manufacturers of America (PhRMA) (link)

Global Genes Latest News Global Genes (link)

Global Genes Rare Daily Global Genes (link)

Global Genes Event Hub Global Genes (link)

Rare Disease Scientific Workshop EveryLife Foundation for Rare Diseases (link)

OrphaNews Orphanet (link)