SCID and Primary Immunodeficiency Fact Sheet

CIRM funds many projects seeking to better understand Severe Combined Immune Deficiency (SCID) and other primary immunodeficiency diseases to translate those discoveries into new therapies.


Primary immunodeficiencies are disease that compromise or destroy the immune system, leaving patients susceptible to serious infections. Typically, these diseases have genetic causes and many of them are rare. Severe combined immune deficiency or SCID is an example of a primary immunodeficiency.

SCID – also known as ‘bubble boy disease’ – is a rare genetic disorder, effecting one in 30,000 newborns. Left untreated the children die before the age of 2, and the only readily available treatment involves high-risk bone marrow transplants. Because these patients already have a compromised immune system, 10 to 20 percent don’t survive the transplant.

Gene therapy has been used to correct the defect in certain types of SCID, but early gene modifying techniques resulted in some patients developing cancer. Newer gene therapy techniques appear to be safer but have been tried on fewer than 20 patients.

Researchers funded by California’s stem cell agency are looking for a better alternative to help these children. They are trying to improve the safety of bone marrow transplant (BMT), which essentially uses the stem cells in bone marrow to give the children a new immune system that works properly. Most of the risk of current BMT procedures comes from the radiation or chemotherapy given to patients before the transplant to wipe out the patient’s own stem cells that form immune cells. These regimens kill many types of cells beyond those intended and result in numerous toxic side effects.

Clinical Stage Programs

Stanford School of Medicine (X-linked SCID)

This team proposes to replace SCID patients’ dysfunctional immune cells with healthy ones using a safer form of bone marrow transplant (BMT). They plan to eliminate the bad cells with an antibody, a protein, that very specifically targets and eliminates blood forming stem cells. If successful, the procedure could open up similar BMT therapies to patients with other auto-immune diseases such as multiple sclerosis, lupus or diabetes that are generally not candidates for BMT currently. These diseases, while debilitating, are not immediately life-threatening and generally don’t warrant the risks involved in BMT the way it is done today.

St. Jude Children’s Research Hospital

The team is using gene therapy to correct a genetic mutation in the blood stem cells of patients with X-linked SCID. The corrected stem cells are then transplanted back into the patient to restore their immune system’s ability to produce healthy immune cells. This will allow the patient to fight off infections and will hopefully cure their disease. 

University of California, Los Angeles (Chronic granulomatous disease and ADA-SCID)

The team is developing a therapy for chronic granulomatous disease: a very rare primary immune deficiency disease that results in severe and recurrent infections that can impact quality and length of life. The UCLA team uses the patient’s own genetically modified blood stem cells to create a new blood supply and immune system to eradicate the problem.

UCLA is also developing a therapy for a form of SCID called adenosine deaminase (ADA)-deficient SCID. Patients with ADA-SCID lack an important enzyme called adenosine deaminase in their immune cells. Without this enzyme, toxic by-products build up in their immune cells and eventually kill them off leaving the patient susceptible to deadly infections. The group from UCLA will genetically modify patient blood stem cells to remove the disease-causing mutation and transplant these corrected stem cells back into the patient to create a new, healthy immune system. 

CIRM Grants Targeting Immune Diseases including SCID

Researcher NameInstitutionGrant TitleGrant TypeAward Amount
Dr. Caroline Y. KuoUniversity of California, Los AngelesEvaluation of Gene Therapy Approaches for Autosomal Recessive Hyper IgE Syndrome Due to Mutations in DOCK8Progression Award – Discovery Stage Research Projects$234,000
Dr. Katja WeinachtStanford UniversityRegenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion SyndromeQuest – Discovery Stage Research Projects$1,251,720
Dr. Rosa BacchettaStanford UniversityGENE EDITING FOR FOXP3 IN HUMAN HSCQuest – Discovery Stage Research Projects$984,228
Dr. Ahmed Gamal IbrahimCedars-Sinai Medical CenterNoncoding RNA drug TY1 as a therapeutic candidate for scleroderma and systemic sclerosisTherapeutic Translational Research Projects$2,590,224
Dr. Caroline Y. KuoUniversity of California, Los AngelesEx Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper-IgM SyndromeTherapeutic Translational Research Projects$4,896,628
Dr. Christel H. UittenbogaartMidwinter Conference of Immunologists62nd Midwinter Conference of ImmunologistsConference II$49,325
Dr. Everett H. MeyerStanford UniversityCellular Immune Tolerance SymposiumConference II$31,225
Dr. Donald B. KohnUniversity of California, Los AngelesPrimary Immune Deficiency Treatment Consortium (PIDTC) Annual Scientific WorkshopConference II$29,807
DR Jonathan BenjaminImmPACT-Bio, Inc.A phase 1/2 study to evaluate a bispecific CD19/CD20-directed CAR T cell, in refractory lupus nephritis and systemic lupus erythematosusClinical Trial Stage Projects$8,000,000
Steven G. DeeksUniversity of California, San FranciscoAnti-HIV duoCAR-T cell therapy for HIV infectionClinical Trial Stage Projects$8,970,732
Dr. Kinnari PatelRocket Pharmaceuticals, Inc.LADICellClinical Trial Stage Projects$5,867,085
Stephen GottschalkSt. Jude Children’s Research HospitalLentiviral Gene Therapy for Infants with X-linked Severe Combined Immunodeficiency using Autologous Bone Marrow Stem Cells and Busulfan ConditioningClinical Trial Stage Projects$11,924,780
Dr. Donald B. KohnUniversity of California, Los AngelesEfficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjectsClinical Trial Stage Projects$5,827,000
Leslie MeltzerOrchard Therapeutics plcEfficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjectsClinical Trial Stage Projects$2,638,745
Dr. Donald B KohnUniversity of California, Los AngelesEfficacy and safety of cryopreserved autologous CD34+ HSC transduced with EFS lentiviral vector encoding for human ADA gene in ADA-SCID subjectsClinical Trial Stage Projects$10,156,925
Dr. Donald B. KohnUniversity of California, Los AngelesA Phase I/II, Non Randomized, Multicenter, Open-Label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous DiseaseClinical Trial Stage Projects$7,083,364
Dr. Brian JohnstoneOssium Health, Inc.Development of OSSM-007, cryopreserved interferon-gamma primed allogeneic MSCs, for treatment of steroid refractory acute graft versus host diseaseLate Stage Preclinical Projects$3,457,858
Dr. Rosa BacchettaStanford UniversityIND-enabling activities for a Phase 1 Study of Autologous CD4LVFOXP3 T Cells in Subjects with IPEX SyndromeLate Stage Preclinical Projects$5,002,496
Dr Jennifer M PuckUniversity of California, San FranciscoEx Vivo Transduction of the Human Artemis (DCLRE1C) cDNA by Lentiviral Vector AProArt into CD34+ Hematopoietic Cells for Artemis (ART)-Deficient Severe Combined Immunodeficiency (SCID)Late Stage Preclinical Projects$4,268,865
Dr. Matthew H PorteusStanford UniversityPre-clinical development of gene correction therapy of hematopoietic stem cells for SCID-X1Preclinical Development Awards$874,877
Dr. Mark S. AndersonUniversity of California, San FranciscoGeneration of a functional thymus to induce immune tolerance to stem cell derivativesBasic Biology V$1,191,000
Dr. Judith A ShizuruStanford UniversityA monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplantsDisease Team Therapy Development – Research$18,990,683
Mort CowanUniversity of California, San FranciscoGene Correction of Autologous Hematopoietic Stem Cells in Artemis Deficient SCIDEarly Translational III$3,862,367
Dr. Judith A ShizuruStanford UniversityA monoclonal antibody that depletes blood stem cells and enables chemotherapy free transplantsDisease Team Therapy Planning I$90,147
Dr. David Louis DiGiustoCity of Hope, Beckman Research InstituteDevelopment of RNA-based approaches to stem cell gene therapy for HIVEarly Translational II$3,097,160
Dr. Inder M. VermaSalk Institute for Biological StudiesCuring Hematological DiseasesEarly Translational I$5,979,252
Dr. Ellen A. RobeyUniversity of California, BerkeleyHuman Immune System Mouse models as preclinical platforms for stem cell derived graftsTransplantation Immunology$1,005,605
Dr. Nicholas R.J. GascoigneScripps Research InstituteRole of Innate Immunity in hematopoeitic stem cell-mediated allograft toleranceTransplantation Immunology$1,705,554
Dr. Kenneth WeinbergStanford UniversityEngineered immune tolerance by Stem Cell-derived thymic regenerationTransplantation Immunology$1,271,729
Dr. Yang XuUniversity of California, San DiegoInduction of immune tolerance to human embryonic stem cell-derived allograftsTransplantation Immunology$1,192,680
Dr. Gay Miriam CrooksUniversity of California, Los AngelesEngineering Thymic Regeneration to Induce ToleranceTransplantation Immunology$1,235,445
Dr. Husein HadeibaPalo Alto Veterans Institute for ResearchApplication of Tolerogenic Dendritic Cells for Hematopoietic Stem Cell TransplantationTransplantation Immunology$733,061
Dr. Anjana RaoLa Jolla Institute for Allergy and ImmunologyGeneration of regulatory T cells by reprogrammingTransplantation Immunology$1,464,446
Dr. Tippi C. Mackenzie MDUniversity of California, San FranciscoMaternal and Fetal Immune Responses to In Utero Hematopoietic Stem Cell TransplantationTransplantation Immunology$1,230,869
Dr. Jeanne F LoringScripps Research InstituteThymus based tolerance to stem cell therapiesTransplantation Immunology$1,108,921
Dr. Judith A ShizuruStanford UniversityPurified allogeneic hematopoietic stem cells as a platform for tolerance inductionTransplantation Immunology$1,233,275
Dr. Jeffrey A BluestoneUniversity of California, San FranciscoStem cell tolerance through the use of engineered antigen-specific regulatory T cellsTransplantation Immunology$1,152,768
Dr. Mark S. AndersonUniversity of California, San FranciscoStem cell differentiation to thymic epithelium for inducing tolerance to stem cellsTransplantation Immunology$1,314,089
Dr. Michele CalosStanford UniversitySafe, efficient creation of human induced pluripotent stem cells without the use of retrovirusesNew Cell Lines$1,406,875
Dr. Irving L Weissman MDStanford UniversityProspective isolation of hESC-derived hematopoietic and cardiomyocyte stem cellsComprehensive Grant$2,471,386
Dr. Jerome A. Zack Ph.D.University of California, Los AngelesHuman Embryonic Stem Cell Therapeutic Strategies to Target HIV DiseaseComprehensive Grant$2,401,903
Dr. Samuel PleasureUniversity of California, San FranciscoHuman stem cell derived oligodendrocytes for treatment of stroke and MSComprehensive Grant$2,459,235
Thomas Edward LaneUniversity of California, IrvineHuman Embryonic Stem Cells and Remyelination in a Viral Model of DemyelinationSEED Grant$368,081
Dr. Kenneth WeinbergStanford UniversityEmbryonic stem cell-derived thymic epithelial cellsSEED Grant$628,793
Dr. Irvin SY ChenUniversity of California, Los AngelesGenetic modification of the human genome to resist HIV-1 infection and/or disease progressionSEED Grant$616,800
Dr. Irvin SY ChenUniversity of California, Los AngelesHPSC based therapy for HIV disease using RNAi to CCR5.Disease Team Research I$9,905,604
Prof. John A ZaiaCity of Hope, Beckman Research InstituteZINC FINGER NUCLEASE-BASED STEM CELL THERAPY FOR AIDSDisease Team Research I$14,536,969


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