Can gene therapy help treat sickle cell? 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Health experts are exploring gene therapy as a potentially new treatment to manipulate gene expression. With this technique, it may be possible to restore the shape of red blood cells (RBCs) and eliminate SCD complications. SCD is a group of genetic RBC disorders that affects roughly 100,000 people in the United States. At present, most treatments aim to reduce symptoms and complications. However, advances in gene therapy may offer a new curative approach. In this article, we will discuss gene therapy and its potential role in treating sickle cell disease. Definitions Share on Pinterestangelp/Getty ImageSCD is an inherited RBC condition. A person with SCD has a gene alteration in the hemoglobin beta (HBB) gene present on chromosome 11. Hemoglobin is an iron-rich protein in RBCs that gives them their shape and helps transport oxygen. Healthy RBCs are round and flexible, allowing them to travel through blood vessels. However, in people with SCD, RBCs are rigid and shaped like a “C” or sickle, which is how the condition gets its name. As these C-shaped cells are misshapen, the body breaks them down more quickly than healthy RBCs. They can also become stuck and interrupt blood flow, which can cause pain and infections. There are several types of SCD, depending on what genes biological parents pass on. The most common types include:sickle cell anemiahemoglobin C diseasesickle cell beta-thalassemia Gene therapy refers to a medical approach that aims to treat genetic conditions. This technique modifies gene expression to prevent gene changes from causing symptoms of a disease. Different mechanisms are available and may include:replacing the gene causing the disease with a healthy copyinactivating the disease-causing gene if it is not functioning properlyintroducing a new or modified gene to help treat the condition How gene therapy may treat sickle cell Gene therapy aims to treat genetic diseases by providing cells with a new set of instructions to change how they function, with the aim of correcting the condition. SCD results from alterations in the HBB gene, which produces the protein beta-globin. By adding a new version of this gene, it may be possible to prevent RBCs from developing a sickle shape. To begin this therapy, doctors will first collect stem cells either from a person’s bone marrow or a blood sample using a medication called plerixafor. This drug helps move stem cells from the bone marrow into the bloodstream. The doctors will modify these stem cells outside of the body. Doctors then need a carrier to transport the new genetic material into the stem cells — they call this carrier a vector. Usually, the vector will be a virus that health experts have modified to make harmless and instead carry the new genes. Similar to how viruses replicate by injecting genetic material into living cells, the modified viruses insert the new genes into stem cells. Before a person can receive these new stem cells, they first undergo a procedure called conditioning. Conditioning uses chemotherapy to create space in the bone marrow for the new stem cells. A person will then receive a blood infusion containing the new stem cells. Researchers are also investigating a technique known as gene editing to treat SCD. Gene editing works by adding, removing, or altering genetic material to change how cells work. One of the main approaches for treating SCD is to encourage the production of fetal hemoglobin (HbF). This type of hemoglobin is present in a fetus but becomes suppressed as the child ages. Unlike adult hemoglobin, the altered sickle cell gene does not affect HbF. Gene editing aims to stop the suppression of HbF by targeting a gene called BCL11A. By suppressing this gene, the body can resume producing HbF and, as a result, have healthy RBCs. This type of gene therapy involves similar steps of collection, a vector, and an infusion. However, instead of delivering new genetic material, the vector transports a gene editing technology called CRISPR/Cas9 to interrupt the BCL11A gene. Although SCD will still be able to affect some of the RBCs in the body after this treatment, research estimates that a 20% level of HbF in the bloodstream can be enough to improve SCD symptoms. Studies and trials New advances in gene therapy have led to several studies and trials that show promising results for the potential treatment of SCD. A 2022 study investigated the effectiveness of a gene therapy for SCD called LentiGlobin and found that a one-time treatment led to a sustained increase in nonsickling hemoglobin in participants’ blood. This treatment led to a reduction in hemolysis and resolution of severe vaso-occulusive events. This refers to a type of sickle cell crisis, where sickled RBCs block blood flow and cause severe complications. A 2019 study notes a successful trial using a modified vector to transfer a healthy HbF gene to people with SCD. In both cases of using this technique, individuals saw improvements in the SCD symptoms. Similarly, a 2021 study notes a successful trial where CRISPR/Cas9 gene editing techniques were successful in targeting the BCL11A gene. After treatment, the individual had higher levels of HbF and no vaso-occlusive episodes. Although gene therapy research for SCD is ongoing, early trials seem to be yielding positive results. The technique can potentially increase the level of healthy, functioning hemoglobin and reduce severe pain crises. Potential risks A potential risk from gene therapy comes from the need for a person to undergo chemotherapy beforehand to prepare their body for new stem cells. Potential side effects of chemotherapy may include:nausea and loss of appetitehair losshigher risk of infertilityincreased risk of cancer There have also been cases of participants developing leukemia and myelodysplastic syndrome after gene therapy for their SCD. However, the research is inconclusive as to whether this occurs due to the chemotherapy conditioning, the gene therapy itself, or because people with SCD may have a higher risk of these cancers. Current limitations Since health experts tailor gene therapy specifically for each individual using their own cells, it is a time-consuming and expensive procedure. This high cost may significantly limit its availability for many people. A further limitation is that since research into new gene therapy techniques is still new, healthcare professionals do not fully understand the long-term effects and safety of these treatments. Other treatments The only current curative treatment available for SCD is a bone marrow transplant. This procedure works similarly to gene therapy, but the healthy RBCs come from the bone marrow of a compatible donor. Other treatments aim to manage symptoms, lower the frequency of sickle cell crises, and reduce the risk of complications. Such treatments may include:blood transfusionhydroxyurea (Hydrea)crizanlizumab (Adakveo)voxelator (Oxbryta)pain medication, such as L-glutamine, acetaminophen, or ibuprofen penicillin and other medications to reduce infection risk Summary Sickle cell disease is a group of genetic conditions that affects hemoglobin. These genetic alterations result in health complications, as red blood cells cannot function correctly. Gene therapy is a potentially curative treatment that aims to encourage the production of more healthy RBCs to alleviate symptoms. Although trials are still ongoing and the long-term effects are still unclear, promising results show the potential for gene therapy as a treatment option. Last medically reviewed on July 28, 2022GeneticsBlood / HematologyClinical Trials / Drug Trials 27 sourcescollapsedMedical News Today has strict sourcing guidelines and draws only from peer-reviewed studies, academic research institutions, and medical journals and associations. We avoid using tertiary references. We link primary sources — including studies, scientific references, and statistics — within each article and also list them in the resources section at the bottom of our articles. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.About sickle cell disease. (2020). https://www.genome.gov/Genetic-Disorders/Sickle-Cell-DiseaseBlood and marrow transplant vs. gene therapy. (n.d.). https://www.chop.edu/centers-programs/sickle-cell-and-red-cell-disorders-curative-therapy-center-cured/blood-and-marrow-transplant-vs-gene-therapyBorhade, M. B., et al. (2021). Sickle cell crisis. https://www.ncbi.nlm.nih.gov/books/NBK526064/Catlin, N. (2019). Initial data shows potential of gene therapy for sickle cell anemia. https://journals.lww.com/oncology-times/fulltext/2019/02051/initial_data_shows_potential_of_gene_therapy_for.7.aspxCurtis, S., et al. (2020). Gene therapy in sickle cell disease: Possible utility and impact. https://www.researchgate.net/profile/Susanna-Curtis/publication/338786102_Gene_therapy_in_sickle_cell_disease_Possible_utility_and_impact/links/5e416317458515072d8f8ed6/Gene-therapy-in-sickle-cell-disease-Possible-utility-and-impact.pdfEsrick, E. B., et al. (2021). Post-transcriptional genetic silencing of bcl11a to treat sickle cell disease. https://www.nejm.org/doi/full/10.1056/NEJMoa2029392Fetal hemoglobin (hemoglobin F). (n.d.). https://health.maryland.gov/phpa/genetics/Pages/hemo_f.aspxFrangoul, H., et al. (2021). CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. https://www.nejm.org/doi/full/10.1056/NEJMoa2031054Gene therapy program: SCD. (n.d.). https://www.childrenshospital.org/programs/gene-therapy-program/conditions-we-treat/scdGenetic therapy conditioning: Patient guide. (2021). https://curesickle.org/system/files/CSC_Conditioning_Patient_Bi_FOLD_FactSheet_042321_Digital_CenterSpread.pdfHBB gene. (2020). https://medlineplus.gov/genetics/gene/hbb/How does gene therapy work? (2022). https://medlineplus.gov/genetics/understanding/therapy/procedures/Jones, R. J., et al. (2021). Leukemia after gene therapy for sickle cell disease: Insertional mutagenesis, busulfan, both, or neither [Abstract]. https://pubmed.ncbi.nlm.nih.gov/34115136/Kanter, J., et al. (2021). Gene therapy for sickle cell disease: Where we are now? https://ashpublications.org/hematology/article/2021/1/174/482932/Gene-therapy-for-sickle-cell-disease-where-we-areKanter, J., et al. (2022). Biologic and clinical efficacy of LentiGlobin for sickle cell disease. https://www.nejm.org/doi/full/10.1056/NEJMoa2117175LentiGlobin for sickle cell disease [Video]. (2022).https://www.youtube.com/watch?v=TgC4VYhRU9ARedman, M., et al. (2016). What is CRISPR/cas9? https://ep.bmj.com/content/101/4/213Sickle cell disease. (2017). https://rarediseases.org/rare-diseases/sickle-cell-disease/Sickle cell disease. (n.d.). https://www.hematology.org/education/patients/anemia/sickle-cell-diseaseSickle cell disease (SCD). (2022). https://www.cdc.gov/ncbddd/sicklecell/index.htmlSickle cell disease: Treatment. (2022). https://www.nhlbi.nih.gov/health/sickle-cell-disease/treatmentUchida, N., et al. (2020). Safe and efficient peripheral blood stem cell collection in patients with sickle cell disease using plerixafor. https://www.haematologica.org/article/view/9644What are genome editing and CRISPR-Cas9. (2022). https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/What is gene therapy? (2022). https://medlineplus.gov/genetics/understanding/therapy/genetherapy/What is gene therapy? (2018). https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapyWhat is genome editing? (2019). https://www.genome.gov/about-genomics/policy-issues/what-is-Genome-EditingWhat is sickle cell disease (SCD)? (n.d.).https://www.sicklecelldisease.org/sickle-cell-health-and-disease/types/FEEDBACK:Medically reviewed by Julie Scott, DNP, ANP-BC, AOCNP — By Flynn Williams on July 28, 2022 Latest newsWhat sets 'SuperAgers' apart? 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