Gene-therapy history
1962: Gene therapy is born
Professor William Szybalski shows that a genetic mutation can be corrected by adding DNA into an animal cell.1
1975: The Asilomar Conference
In light of global skepticism around genetic modification, scientists, journalists, and government officials from around the world meet in California to discuss the future of gene technology. Despite disapproval by some well-known members, the conference ends with the decision to continue gene technology research with the enforcement of a strict set of rules.3
1993: Discovery of CRISPR
Professor Francisco Mojica finds DNA in bacteria with unique repeating structures, later to be known as clustered regularly interspaced short palindromic repeats (CRISPR).4
1999-2000: Setbacks for gene therapy
Gene-therapy patient Jesse Gelsinger dies after an unexpected immune reaction to the gene’s delivery vehicle. The next year, 2 clinical trials of gene therapy in the UK and France result in 5 out of 20 male patients developing leukemia from uncontrolled mutations in their DNA.5-7
2000: National Gene Transfer Research Safety Symposia initiated
The first symposium is convened to discuss new safety protocols to enhance the protection of research participants in gene transfer clinical trials.8
2000: FDA and NIH plan new safety initiatives
The US Food and Drug Administration (FDA) and National Institutes of Health (NIH) cooperate to enforce more transparency in gene-therapy clinical trials, as well as adherence to existing guidelines, to improve safety for trial participants.9
2005: ZFNs studied for gene modification
Zinc-finger nucleases (ZFNs), first discovered in the African clawed frog, are shown to modify the x-linked severe combined immune deficiency (SCID) mutation in a human’s IL2Rγ gene, giving hope to the possible use of ZFNs in treating diseases.10-12
2011: Plant pathogens successfully modify human cells
Transcription activator-like effector nucleases (TALENs), engineered plant pathogens known for their high safety record in gene editing, are used for the first time in clinical trials to safely modify the human genome.13-15
2012: Discovery of third-generation gene-editing tool
Scientists Emmanuelle Charpentier and Jennifer A. Doudna reprogram the ancient defenses of toxic bacteria to make precise cuts to any DNA molecule for gene editing. These low-cost genetic snipping tools are aptly named CRISPR/Cas9 genetic scissors.16-18
2012: First approval of gene-addition therapy in the EU
The European Medicines Agency approves the first gene-addition therapy to treat patients with the rare genetic disorder known as lipoprotein lipase (LPL) deficiency.19,20
2012: FDA approval of first HPC, cord blood
FDA approves ClinImmune allogeneic cord blood hematopoietic progenitor cell therapy for use in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.21
2013: FDA approval of second HPC, cord blood
FDA approves LifeSouth allogeneic cord blood hematopoietic progenitor cell therapy indicated for use in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.22
2016: FDA approval of third HPC, cord blood
FDA approves Bloodworks allogeneic cord blood hematopoietic progenitor cell therapy for use in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.23
2017: First FDA-approved gene therapy
The FDA approves KYMRIAH® (tisagenlecleucel), the first gene therapy available in the United States, indicated for certain patients with acute lymphoblastic leukemia.24
2017: FDA approval of first CAR T-cell therapy
The FDA approves Yescarta® (axicabtagene ciloleucel) T-cell therapy indicated for adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.25
2017: FDA approval of in-vivo gene-addition therapy
The FDA approves LUXTURNA® (voretigene neparvovec-rzyl), an in-vivo gene-addition treatment using viral vectors. The therapy is designed to replace a dysfunctional gene in visually impaired patients to improve their eyesight.26,27
2018: FDA approval of fourth HPC, cord blood
FDA approves MD Anderson Cord Blood Bank allogeneic cord blood hematopoietic progenitor cell therapy for use in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.28
2019: FDA approval of second gene-addition therapy
The FDA approves ZOLGENSMA® (onasemnogene abeparvovec-xioi), an in-vivo gene-addition treatment using viral vectors. The therapy is indicated for certain pediatric patients with spinal muscular atrophy.29
2020: FDA approval of second CAR T-cell therapy
The FDA approves TECARTUS® (brexucabtagene autoleucel) T-cell immunotherapy indicated for adult patients with relapsed or refractory mantle cell lymphoma (MCL) and adult patients with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic lymphoma (ALL).30
2021: Gene-therapy clinical trials expand
An ever-growing number of clinical trials are underway to test the effectiveness of gene-addition and gene-editing approaches in treating a variety of blood disorders, cancers, and other complex diseases.31
2022: FDA approval of third gene-addition therapy
The FDA approves ZYNTEGLO® (betibeglogene autotemcel), an ex-vivo gene-addition treatment indicated for adult and pediatric patients with β-thalassemia who require regular red blood cell (RBC) transfusions.32
2022: FDA approval of third CAR T-cell therapy
The FDA approves two new indications for Breyanzi® (lisocabtagene maraleucel) T-cell therapy indicated for adult patients with large B-cell lymphoma (LBCL) who have: refractory disease to first-line chemoimmunotherapy or relapse within 12 months, or refractory disease to first-line chemoimmunotherapy or relapse and not eligible for hematopoietic stem cell transplantations (HSCT).33
2022: FDA approval of one-time gene therapy
The FDA approves SKYSONA® (elivaldogene autotemcel) one-time gene therapy indicated for certain pediatric patients to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD).34
2022: FDA approval of virus vector-based gene therapy
The FDA approves HEMGENIX® (etranacogene dezaparvovec-drbl) of adeno-associated virus vector-based gene therapy indicated for adult patients with hemophilia B (congenital Factor IX deficiency) who currently use Factor IX prophylaxis therapy, have current or historical life-threatening hemorrhage, or spontaneous bleeding episodes.35
2022: FDA approval of non-replicating gene therapy
The FDA approves ADSTILADRIN® (nadofaragene firadenovec-vncg) non-replicating adenoviral vector-based gene therapy indicated for adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.36
2023: FDA approval of T-cell immunotherapy
The FDA approves CARVYKTI® (ciltacabtagene autoleucel) T-cell immunotherapy indicated for adult patients with relapsed or refractory multiple myeloma who previously received four or more prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 antibody.37
2023: FDA approval of cord blood-derived cell therapy
The FDA approves OMISIRGE® (omidubicel-onlv) cell therapy derived from cord blood indicated for adult and pediatric patients 12 years and older with hematologic malignancies following myeloablative conditioning.38
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