Lentiviral gene therapy for treating FHL3 patients (Munc)
Other informations
Gene therapy
Hemophagocytic lymphohistiocytosis (HLH)
Genotype Phenotype
Cohorts
Pediatric and Adult
<10
TNGS / WES / WGS*
CEDI
Observational trials
NCT02113917: formation of a Cohort of HLHa Patients in Order to Study Their Physiopathological Characteristics
Patient samples
Peripheral Blood Lymphocytes
Targets
In vitro models
T cells
Macrophages
In vivo models
STX11 KO mice
conditionnal STX11 flox/flox mice
conditionnal STXBP2 KO mice
Specific targets
PRF1, RAB27A, UNC13D, STX11, STXBP2, LYST
Therapeutics
Protocols/Technics
T cell degranulation and killing analysis
Immune synapse formation analysis
Evaluation of the innate immune response
Evaluation of the viral infection (LCMV)
Clinical trials
NCT
NCT02472054: phase I/II treatment of Familiar Lymphohistiocytosis (C-HLH)
NCT02069899 : multicenter Study for the Long-term Follow-up of HLH Patients Who Received Treatment With NI-0501, an Anti-interferon Gamma Monoclonal Antibody
V(D)J recombination analysis for the identification of NHEJ inhibitors
Clinical trials
Ataxia-telangiectasia (AT)
Genotype Phenotype
Cohorts
ImmuneRep: pediatric and adult
45
TNGS / WES / WGS*
PID_Diag.V2
Patient samples
RNA
Targets
In vitro models
ProB murine cell lines
Specific targets
ATM
Therapeutics
Specific biomarkers
Promidis alpha: diagnostic biomarkers
Protocols/Technics
V(D)J recombination analaysis for the identification of NHEJ inhibitors
Clinical trials
Cernunnos-XLF deficiency
Genotype Phenotype
Cohorts
ImmuneRep: Pediatric
10
TNGS / WES / WGS*
CEDI
Patient samples
Fibroblasts
RNA
Targets
In vitro models
SV40 fibroblasts
ProB murine cell lines
In vivo models
C57Bl/6J CRISPR-XLF KO mice
C57Bl/6J CRISPR-XLF conditional KO mice
Specific targets
XRCC4-like factor (XLF, cernunnos)
Therapeutics
Specific biomarkers
Promidis alpha: diagnostic biomarkers
Protocols/Technics
V(D)J recombination analaysis for the identification of NHEJ inhibitors
Clinical trials
Combined immunodeficiency-enteropathy spectrum
Genotype Phenotype
Cohorts
Pediatric and Adult
<100
TNGS / WES / WGS*
CEDI
Observational trials
NCT02909244: study of Gut Microbiota in Primary Immune Deficiency, Possibly Associated With Inflammatory Bowel Disease (DIPobiota)
Patient samples
Peripheral Blood Lymphocytes
Targets
In vitro models
T cells
Dendritic cells
In vivo models
TTC7A GFP
TTC7A KO mice
TTC7A KI mice
Specific targets
TTC7A
Therapeutics
Clinical trials
Coronin 1A deficiency
Genotype Phenotype
Cohorts
Isolated pediatric cases
2
TNGS / WES / WGS*
CEDI
Targets
Specific targets
CORO1A
Therapeutics
Protocols/Technics
V(D)J recombination analaysis for the identification of NHEJ inhibitors
Clinical trials
CTPS1 deficiency
Genotype Phenotype
Cohorts
Pediatric
Less than 10
TNGS / WES / WGS*
CEDI
Observational trials
Martin E et al. Nature. 2014 Jun 12;510(7504):288-92
Patient samples
PBMC
Fibroblasts
Targets
In vitro models
CTPS1 inactivation (KO HEK, KO JURKAT)
CTPS2 inactivation (KO HEK)
CTPS1 and CTPS2 inactivation (double KO HEK)
CTPS1 KO HEK complemented with CTPS1-GFP/DesRED
CTPS1 KO JURKAT complemented with CTPS1-GFP
CTPS2 KO HEK complemented with CTPS2-GFP/DesRED
CTPS2 KO JURKAT complemented with CTPS2-GFP
CTPS1 KO JURKAT complemented with CTPS1 mutants
In vivo models
CTPS1 inactivation (conditional KO mice
cre-CMV (all tissues)
cre-VAV1 (hematopoietic tissues)
cre-CD8 (CD8+ cells)
cre-CD4+ (thymocytes CD4+CD8+))
CTPS1 inactivation (KI mice mimicking human mutation)
CTPS1 inductible (KO mice under tamoxifen treatment)
CTPS2 inactivation (conditional KO mice under cre-CMV)
Protocols/Technics
Detection of CTPS1 by FACS and WB
Screening cascade on HEK, JURKAT and PBMC
Specific targets
CTPS1
RASGRP1
Therapeutics
Clinical trials
DNA ligase IV deficieny
Genotype Phenotype
Cohorts
ImmuneRep: pediatric
10
TNGS / WES / WGS*
CEDI
Patient samples
Fibroblasts
RNA
Targets
In vitro models
SV40 fibroblasts
ProB murine cell lines
In vivo models
XRCC4 KO mice
XRCC4 KI mice
Specific targets
LIG4
XRCC4
Therapeutics
Specific biomarkers
Promidis alpha: diagnostic biomarkers
Protocols/Technics
V(D)J recombination analaysis for the identification of NHEJ inhibitors
Clinical trials
Hoyeraal-Hreidarsson Syndrome (HHS)
Genotype Phenotype
Cohorts
ImmuneRep: pediatric
20
TNGS / WES / WGS*
CEDI
Patient samples
Fibroblasts
Targets
In vitro models
Fibroblasts
SV40 fibroblasts
SV40-hTERT fibroblasts
B-EBV fibroblasts
In vivo models
Apollo KO mice
Apollo KI mice
PARN KO mice
PARN KI mice
Specific targets
DCLRE1B/SNM1B/Apollo
DKC1
PARN
Therapeutics
Specific biomarkers
Promidis alpha: diagnostic biomarkers
Protocols/Technics
Telomere restriction fragment (TRF) analysis
Clinical trials
RAD50 deficiency
Genotype Phenotype
Cohorts
Isolated pediatric case
1
Patient samples
Fibroblasts
Targets
In vitro models
Fibroblasts
SV40-fibroblasts
SV40-hTERT fibroblasts
B-EBV
In vivo models
RAD50 KI mice
Specific targets
RAD50
Therapeutics
Clinical trials
RAG1/2 deficiency
Genotype Phenotype
Cohorts
ImmuneRep: Pediatric and Adult
100
TNGS / WES / WGS*
CEDI
Patient samples
Fibroblasts
Targets
In vitro models
ProB murine cell lines
Specific targets
RAG1
RAG2
Therapeutics
Specific biomarkers
Promidis alpha: diagnostic biomarkers
Protocols/Technics
V(D)J recombination analaysis for the identification of NHEJ inhibitors
Clinical trials
Severe Combined Immunodeficiency (SCID) X1
Genotype Phenotype
Targets
Specific targets
γc-deficiency
Therapeutics
Specific therapeutic approaches
Gene therapy
Clinical trials
NCT
NCT03879876 : phase I/II safety and efficacy study of human T lymphoid progenitor (HTLP) injection after partially HLA compatible allogeneic hematopoietic stem cell transplantation in SCID patients (HTLP Necker)
NCT01410019: phase I/II gene therapy for X-linked severe combined immunodeficiency (SCID2)
Shwachman-Diamond Syndrome (SDS)
Genotype Phenotype
Cohorts
Pediatric and adults
20
Patient samples
Fibroblasts
Targets
In vitro models
Fibroblasts
SV40-fibroblasts
SV40-hTERT fibroblasts
B-EBV
Specific targets
SBDS
Therapeutics
Protocols/Technics
V(D)J recombination analaysis for the identification of NHEJ inhibitors
Compensatory somatic mutation creation analysis in leukemogenesis
Clinical trials
Immune dysregulation with immunodeficiency
Aicardi-Goutières syndrome (AGS)
Genotype Phenotype
Cohorts
Mainly pediatric
>100
TNGS / WES / WGS*
Interferonopathies
Patient samples
DNA
RNA
Serum/plasma
CSF
PBMCs
Fibroblasts
LCLs
Targets
In vitro models
HEK
HELA
THP1
Protocols/Technics
Singe-cell transcriptomics
CITE-seq protocol
Network inference analysis
Specific targets
TREX1
RNASEH2A
RNASEH2B
RNASEH2C
Therapeutics
Clinical trials
NCT
NCT02363452: phase II Pilot Clinical Trial of Reverse Transcriptase Inhibitors in Children With Aicardi-Goutières Syndrome (AGS)