Nature Communications (Jun 2022)
Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency
- Suk See De Ravin,
- Siyuan Liu,
- Colin L. Sweeney,
- Julie Brault,
- Narda Whiting-Theobald,
- Michelle Ma,
- Taylor Liu,
- Uimook Choi,
- Janet Lee,
- Sandra Anaya O’Brien,
- Priscilla Quackenbush,
- Tyra Estwick,
- Anita Karra,
- Ethan Docking,
- Nana Kwatemaa,
- Shuang Guo,
- Ling Su,
- Zhonghe Sun,
- Sheng Zhou,
- Jennifer Puck,
- Morton J. Cowan,
- Luigi D. Notarangelo,
- Elizabeth Kang,
- Harry L. Malech,
- Xiaolin Wu
Affiliations
- Suk See De Ravin
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Siyuan Liu
- Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
- Colin L. Sweeney
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Julie Brault
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Narda Whiting-Theobald
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Michelle Ma
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Taylor Liu
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Uimook Choi
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Janet Lee
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Sandra Anaya O’Brien
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Priscilla Quackenbush
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Tyra Estwick
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Anita Karra
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Ethan Docking
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Nana Kwatemaa
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Shuang Guo
- Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
- Ling Su
- Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
- Zhonghe Sun
- Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
- Sheng Zhou
- Experimental Cell Therapeutics Lab, St. Jude Children’s Research Hospital
- Jennifer Puck
- Division of Allergy Immunology and Blood and Marrow Transplantation, Department of Pediatrics, University of California San Francisco and UCSF Benioff Children’s Hospital
- Morton J. Cowan
- Division of Allergy Immunology and Blood and Marrow Transplantation, Department of Pediatrics, University of California San Francisco and UCSF Benioff Children’s Hospital
- Luigi D. Notarangelo
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Elizabeth Kang
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Harry L. Malech
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- Xiaolin Wu
- Laboratory of Clinical Immunology and Microbiology, NIAID, NIH
- DOI
- https://doi.org/10.1038/s41467-022-31344-x
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 15
Abstract
De Ravin et al. report an unplanned interim analysis of a secondary safety outcome for an ongoing clinical trial on lentiviral gene therapy for the treatment of X-linked Severe Combined Immunodeficiency (NCT01306019). Vector induced alternative splicing events are identified that cause aberrant fusion transcripts, leading to clonal dominance in a single patient and clonal expansion in others. This can be mitigated by the removal of the lentivector cryptic splice acceptor.
