Caroline Kuo
Email Address:
ckuo@mednet.ucla.edu
Office Phone Number:
(310) 825-6481
UCLA Profile
UCLA Profile
Office Address:
MDCC 12-430
Assistant Professor-in-Residence, Pediatrics
Gene Modification of Human Hematopoietic Stem Cells for the Treatment of Primary Immune Deficiencies Site-specific gene insertion of corrective DNA cassettes enabled by CRISPR/Cas9 in human hematopoietic stem cells (HSC) is becoming a realistic and promising approach for the treatment of many monogenic diseases of the blood system, including primary immune deficiencies and hemoglobinopathies. Targeted integration of an entire cDNA or mini-gene through homology-directed repair (HDR) is particularly attractive for conditions in which diverse pathogenic mutations are distributed across the gene, and for which precise regulation of expression of the gene is needed and may be achieved using endogenous control elements. The Kuo Lab has been investigating this approach for several inborn errors of immunity and expanding this work to other gene editing technologies such as base editors and PRIME editing.
A selected list of publications:
Kuo CY, Chase J, Garcia-Lloret M, Stiehm ER, Moore T, Aguilera MJ, Siles JL, Church JA. Newborn Screening for Severe Combined Immunodeficiency Does Not Identify Bare Lymphocyte Syndrome. J Allergy Clin Immunol. 131(6); 1693-1695. 2013.
Kuo CY, Garcia-Lloret MI, Slev P, Bohnsack JF, Chen K. Profound T-cell Lymphopenia Associated with Prenatal Exposure to Purine Antagonists Detected by TREC Newborn Screening. J Allergy Clin Immunol Pract. 2017 Jan-Feb;5(1):198-200.
Kohn LA, Long JD, Trope EC, Kuo CY. Novel Compound Heterozygote Variations in FADD Identified to Cause FAS-Associated Protein with Death Domain Deficiency. J Clin Immunol. 2020 May; 40(4):658-661.
Kuo CY, Garabedian E, Puck J, Cowan MJ, Sullivan KE, Buckley RH, Cunningham-Rundles C, Marsh R, Candotti F, Kohn DB. Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID) in the US Immunodeficiency Network (USIDNet) Registry. J Clin Immunol. 2020 Nov;40(8):1124-1131.
Kuo CY, Long JD, Campo-Fernandez B, de Oliveira S, Cooper AR, Romero Z, Hoban MD, Joglekar AV, Lill GR, Kaufman ML, Fitz-Gibbon S, Wang X, Hollis RP, Kohn DB. Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome. Cell Reports. 2018 May;23(9):2606-2616.
Romero Z, Lomova A, Miggelbrink A, Kuo CY, Campo-Fernandez B, Hoban MD, Masiuk KE, Clark DN, Long J, Sanchez JM, Velez M, Miyahira E, Zhang R, Brown D, Wang X, Kurmangaliyev YZ, Hollis RP, Kohn DB. Editing the Sickle Cell Disease Mutation in Human Hematopoietic Stem Cells: Comparison of Endonucleases and Homologous Donor Templates. Mol Ther. 2019 Aug
7;27(8):1389-1406.
Gray DH, Villegas I, Long J, Santos J, Keir A, Abele A, Kuo CY, Kohn DB. Optimizing Integration and Expression of Transgenic Bruton’s Tyrosine Kinase for CRISPR-Cas9-Mediated Gene Editing of X-Linked Agammaglobulinemia. CRISPR J. 2021 Apr;4(2):191-206.
Gray DH, Santos J, Keir AG, Villegas I, Maddock S, Trope EC, Long JD, Kuo CY. A comparison of DNA repair pathways to achieve a site-specific gene modification of the Bruton’s tyrosine kinase gene. Mol Ther Nucleic Acids. 2021 Dec 14;27:505-516.
