for people ages 12-35 (full criteria)
at Oakland, California and other locations
study started
completion around
Principal Investigator
by Mark Walters, MD
Headshot of Mark Walters
Mark Walters



This is an open label, non-randomized, 2-center, phase 1/2 trial of a single infusion of sickle allele modified cluster of differentiation (CD34+) hematopoietic stem progenitor cells (HSPCs) in subjects with in subjects ≥12 years old to 35 years old severe Sickle Cell Disease (SCD). The study will evaluate the hematopoietic stem cell transplantation (HSCT) using CRISPR/Cas9 edited red blood cells (known as CRISPR_SCD001 Drug Product).

Official Title

Transplantation of CRISPRCas9 Corrected Hematopoietic Stem Cells (CRISPR_SCD001) in Patients With Severe Sickle Cell Disease


This is an open label, non-randomized, 2-center, phase 1/2 trial of a single infusion of sickle allele modified CD34+ HSPCs in subjects with severe SCD. The primary endpoint of the trial will determine the safety of CRISPR_SCD001 through a 3+3 design with staggered enrollment and a pause in enrollment for safety review after each of the first 3 patients has had drug product infused. After safety is assessed in the 3rd patient, enrollment of the next 3 patients will not be staggered. The first six subjects will be adults. If CRISPR_SCD001 is determined to be safe in the first six subjects, the trial will continue to enroll 3 adolescents 12 - 18 years of age to evaluate the safety in younger patients. The younger age cohort also will follow staggered enrollment.


Sickle Cell Disease, Sickle Cell Anemia, CRISPR_SCD001, CRISPR_SCD001 Drug Product


You can join if…

Open to people ages 12-35

  1. Male or female 12.00 - 34.99 years of age (at time of consent) who have one or more of the following:
    1. History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea);
    2. History of at least 4 severe vaso-occlusive pain events in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea); painful episodes related to or any sickle-related acute event are acceptable; a severe painful vaso-occlusive event is defined as receiving analgesic treatment (opioid or other analgesic) for longer than 24 -hours in a hospital or emergency room (ER) observation unit visit or at least 2 visits in a day unit or ER over 72 hours with both visits requiring intravenous analgesics.
  2. Participants must have adequate physical function as measured by all of the following:
    1. Karnofsky performance score ≥60.
    2. Cardiac function: Left ventricular ejection fraction (LVEF) >40%; or LV shortening fraction > 26% by cardiac echocardiogram or by (multiple-gated acquisition) MUGA scan.
    3. Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥85% and diffusion capacity of lung for carbon monoxide(DLCO) > 40% (corrected for hemoglobin).
    4. Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and estimated or measured creatinine clearance ≥ 70 mL/min/1.73 m2.
    5. Hepatic function:
    6. Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory. Participants with hyperbilirubinemia as the result of hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not excluded.

    ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AS < 5 times upper limit of normal as per local laboratory.

    1. Liver MRI using a validated methodology per institutional preference (T2* or R2* or by ferriscan [R2 MRI]) for estimation of hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions per year for ≥1 year or have received ≥20 packed red blood cell transfusions (lifetime cumulative). Participants who have hepatic iron content ≥ 8 mg Fe/g liver dry weight by liver MRI must have a Gastroenterology/hepatology consultation with liver biopsy and histological examination including documentation of the absence of cirrhosis, bridging fibrosis[1], and active hepatitis.
  3. Written informed consent or assent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

You CAN'T join if...

  1. Participants with uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
  2. Participants with evidence of HIV infection or seropositivity for HIV or active hepatitis B or C.
  3. Participants who have received a Hematopoietic Cell Transplant (HCT)
  4. Participants who have received a solid organ transplant.
  5. Participants who have participated in another clinical trial in which the participant received an investigational or off-label use of a drug or device within 3 months prior to enrollment.
  6. Females who are pregnant or breast feeding.
  7. Females of child bearing potential (to include all female participants > 10 years of age, unless postmenopausal for a minimum of 1 year before the time of consent or surgically sterilized) who do not agree to practice two (2) effective methods of contraception at the same time, or who do not agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject, from the time of signing of informed consent through 12 months post-stem cell infusion.
  8. Males (even if surgically sterilized) who do not agree to practice effective barrier contraception, or who do not agree to practice true abstinence from the time of signing informed consent through 12 months post-stem cell infusion.
  9. Participants who have had a stroke OR who are receiving red blood cell (RBC) transfusions to prevent primary stroke or silent cerebral infarction.
  10. Patients who have a human leukocyte antigen identical (HLA-ID) sibling donor
  11. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  12. Any non-homozygous sickle hemoglobin (HbSS) genotype of SCD


  • UCSF Benioff Children's Hospital
    Oakland California 94609 United States
  • University of California, Los Angeles
    Los Angeles California 90095 United States

Lead Scientist at UCSF

  • Mark Walters, MD
    The over-arching goal of my research career has been to develop and expand curative therapies for hemoglobin disorders in particular and non-malignant hematopoietic disorders more broadly. I have focused on genome editing approaches most recently, which rely upon modification of autologous hematopoietic cells to elicit a curative effect.


not yet accepting patients
Start Date
Completion Date
Mark Walters, MD
Phase 1/2 research study
Study Type
Expecting 9 study participants
Last Updated