The End of the Beginning of Gene Therapy

This marks the first issue of Human Gene Therapy (HGT) published under my stewardship as the new editor-in-chief. Dr. James Wilson's 12-year tenure as editor-in-chief has been overwhelmingly successful, as the field weathered many challenges and more recently has enjoyed a renaissance of interest and opportunity. During Dr. Wilson's tenure, HGT published many high-impact articles, including some of the first demonstrations of clinical efficacy from gene therapy vectors. Under Dr. Wilson's leadership, Human Gene Therapy Methods and Human Gene Therapy Clinical Development were added to the HGT family of journals, and HGT marked its 25th anniversary with a celebration of the pioneers in the field. Indeed, as the first journal in the field, now in existence for 26 years, HGT itself could rightly be counted among the pioneers of gene therapy.

I am very grateful to Mary Ann Liebert, Vicki Cohn, and Jim Wilson for their vote of confidence in my assuming this role, and for the ongoing efforts of Dr. Wilson as he transitions to become editor of Human Gene Therapy Clinical Development. As Dr. Wilson moves into this role at Clinical Development, Barry Byrne will transition to become the U.S. deputy editor, alongside Thierry VandenDriessche, who continues as the European deputy editor. Dr. Guangping Gao will join the team as editor of the parent journal, as Dr. Mark Kay remains within the senior editorial team as associate editor, along with Drs. Ian Alexander and Yu-quan Wei, who remain as associate editors. Finally, Dr. Hildegard Büning will continue on the team as editor of Human Gene Therapy Methods.

In approaching the daunting task of assuming the responsibility to maintain this success, I believe it is more important than ever for the Journal to be clearly committed to its mission: To provide the community of gene therapy investigators with a highly responsive, high-impact journal in which to share results that will ultimately impact human disease . On behalf of myself, the Journal editors, and associate editors, we would like to commit to you to serve that mission: to be rapidly responsive and efficient in handling your submissions, to provide critical review and thus ensure the level of quality that will enhance the visibility and impact of your publications, and to use the Journal as a vehicle to illuminate emerging areas of interest to gene therapy scientists and clinical investigators.

In addition to renewing this commitment to serve as a premier journal for the gene therapy community, the HGT team will seek to emphasize what is unique about the human aspect of our field. The clinical era of human gene therapy has arrived, with quantifiable clinical benefit having been demonstrated with rAAV vectors for genetic disorders of the retina and hemophilia, with lentiviral-mediated CAR-T-cell therapy for cancer, and with gamma retroviral and lentiviral hematopoietic stem cell therapy for a variety of inherited deficits in immunity, hematopoiesis, and metabolism. With the entry into the world of patient care comes an entire new set of considerations for the field. Topics such as clinical trial design, regulatory issues, and biomedical ethics become more central to our field. We hope to reflect that evolution, while continuing to maintain a premier venue for original research in virology, pharmacology, genetics, and molecular biology that underpins all of gene therapy.

In this July special issue, we highlight CRISPR/Cas9-based genome editing, an emerging new part of our field that is exemplary of all of the principles described above. Based on a natural host defense mechanism in bacteria, CRISPR/Cas9 demonstrates a dramatically higher efficiency of precise alteration of genomic DNA than has ever been possible before. In this issue, the contributors review the basic biology of CRISPR in nature, discuss how it has been and will be applied for the creation of better animal models and for therapeutic gene correction, and present original research in the field using this new modality. As described in my editorial in the May issue, the dramatically improved efficiency of gene correction that has been enabled by this technology has forced the field to face some of its most fundamental ethics questions as well. ¹

In the coming months and years, HGT will present other special issues like this one, focusing either on emerging issues or on the work of the gene therapy societies we serve. Beyond the special issues, we will seek to serve as the venue of choice for breakthrough discoveries across the gamut of basic, translational, and clinical research in gene therapy for human disease. As genetic therapies move from the investigational stage to becoming a part of evidence-based medicine, HGT stands ready to be the forum to present that evidence. This represents an incredibly exciting time for the maturation of our field. To quote Winston Churchill, “it is perhaps, the end of the beginning.” ²