Cell and gene therapies (CGTs) are in the vanguard of modern medicine. There are more than 3500 CGTs currently in development targeting a wide array of diseases, including cancer, amyotrophic lateral sclerosis, sickle cell disease, and acquired immune deficiency syndrome, as well as many rare genetic diseases [1]. In the context of this study, we define gene therapy as the therapeutic delivery of nucleic acid into a patient’s cells to treat disease, and cell therapy as the administration of living cells into a patient’s body to treat or cure disease. These broad definitions encompass treatments for a range of diseases that are responsive to CGTs.

By 2030, it is projected that up to 60 new CGTs could be launched that would affect more than 350,000 patients, making such therapies one of the most impactful areas of research and investment in medicine [2,3,4]. The adoption of such therapies is accompanied by a multitude of challenges, and the stakeholders, processes, and outputs involved in CGTs are quite different than traditional pharmaceuticals, necessitating updated approaches for planning, manufacturing, and delivery [5]. A key challenge common to all highly specialized care, including CGTs, is to deliver quality health services to a specific, often small, number of geographically dispersed patients. This is particularly relevant with CGTs, given the associated infrastructural and therapeutic costs from the demand and supply sides. The conventional approach of concentrating clinical, logistical, and infrastructural expertise and capacities in a few large centers of care is not conducive for optimized delivery of CGTs. In low- and middle-income countries (LMICs) in particular, multiple barriers exist to the access to and delivery of CGTs, including inequitable healthcare access, lack of resources, funding shortages, the prohibitive cost of CGTs, and complex regulatory systems [6, 7]. Furthermore, CGT manufacturing, utilization, and access is concentrated in high-income countries. As of 2021, only three of the 20 approved gene therapies worldwide were approved in LMICs [1, 8]. This inequitable landscape of CGTs is worrying, especially given that LMICs carry approximately 90% of the global burden of disease [9]. Concerted efforts are required to expand the delivery of CGTs in LMICs; otherwise, the divide between the disease burden and therapeutic availability will keep growing.

Although it is true that many of the challenges faced by the administration of CGTs are common to other advanced treatments such as bone marrow transplants, CGTs have unique aspects that set them apart. These therapies are often highly personalized, requiring the modification of the patient’s own cells or the design of a therapeutic genetic sequence specific to the patient’s condition. This personalized nature poses unique manufacturing and logistical challenges. Moreover, many CGTs hold the promise of being one-time treatments that can provide lasting benefits, which brings new considerations for cost-effectiveness analyses and reimbursement models. Importantly, CGTs hold substantial potential benefits for LMICs, particularly for diseases prevalent in these areas. For example, gene therapy for β-thalassemia, a prevalent inherited disorder in LMICs, has demonstrated promising results in restoring hemoglobin production and reducing the need for blood transfusions [10]. These unique aspects necessitate specific considerations in the planning, delivery, and post-administration management of CGTs, especially in LMICs. The need to adapt traditional approaches or consider and adopt novel approaches in delivering such therapies is great.

One such approach is the adoption of the hub and spoke healthcare model for delivering CGTs. In a hub and spoke model for healthcare delivery, a main health facility (hub), which receives the most resources and delivers the most intensive services, is complemented with less complex health facilities (spokes), which offer a more limited array of services [5, 11]. Some hub and spoke models also include a partner spoke, a smaller health facility aimed at expanding access to the health services provided by hubs and spokes, especially in rural areas [12]. This model is scalable, efficient, and most importantly, adaptable based on needs and context [13]. The model has been implemented in cancer care to distribute services and improve patient outcomes, in pain management to promote telehealth programs and reach underserved areas, and in acute stroke care to enable remote consultation and timely treatment [12, 14,15,16,17]. In the context of CGTs, traditional delivery models have focused on manufacturing of therapeutic products without full consideration of delivery and access [18, 19]. Recently, calls for delivery of gene therapy, specifically adeno-associated virus–based gene therapy, through hub and spoke models have been observed [20,21,22]. We propose the application of a hub and spoke model for CGT delivery in LMICs, accompanied with a developed framework for core CGT stakeholders. This proposed hub and spoke model is intended to address a wide spectrum of these diseases, which includes inherited conditions, such as certain metabolic disorders, hemophilia, and muscular dystrophy, in which mutations in a single gene can be targeted. It also includes diseases such as cancer, in which gene therapy can be used to modify immune cells to recognize and attack cancer cells, and viral infections, in which gene therapy can potentially be used to target and eliminate the viral genome. In the context of cell therapies, our model may address conditions including cancers in which modified T cells (like CAR-T cells) can be used and autoimmune diseases in which regulatory T cells can potentially restore immune tolerance. This model is then simulated in two distinct scenarios in LMICs: a within-country scenario in Brazil, and a cross-country scenario in the Middle East and North Africa (MENA).

There are a number of emerging treatments that could benefit from our proposed CGT delivery model. Advances in gene editing technologies, such as CRISPR-Cas9, are promising for addressing genetic diseases at their source. Other gene therapies, such as those targeting hemophilia, have already received approval in the Unites States [23], and clinical trials are also being conducted in Brazil. Similarly, CAR-T cell therapies are revolutionizing the treatment of certain cancers and may soon become more prevalent [24,25,26]. Our proposed model could serve as a vehicle to ensure these treatments reach patients in LMICs, further underscoring the relevance and potential of our study.

According to the American Society of Gene & Cell Therapy (ASCGT), 21 CGT clinical trials, nine of which are in phase 3, are underway in Brazil, which is an LMIC as defined by the World Bank [1, 27]. The first CGT-related clinical trial in Brazil was conducted in the early 2000s, after the government developed and implemented more than 10 cellular therapy research centers in recognition of the potential of CGTs [28]. Later developments in the field eventually led to the recent resolution by the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, ANVISA) aimed at regulating the research, development, clinical application, and registration of advanced therapeutic products in Brazil. More recently, ANVISA, in collaboration with the United Nations Development Program, called for the development of the National Network of Specialists in Advanced Therapies (Rede Nacional de Especialistas em Terapias Avançadas, RENETA), a network of experts that support the evaluation of clinical trials, product registration, and monitoring processes of advanced therapeutic products. RENETA also assists in building human capacity at ANVISA to ensure proper regulation over advanced therapeutic products [29]. Thus, Brazil represents a country that is actively engaging with the CGT space. The government’s proactive approach to the development of cellular therapy research centers and its recent regulatory resolutions demonstrates a strong commitment to facilitating the adoption of CGTs.

CGT delivery is still in its infancy in the MENA region. The first record of gene therapy administration in this region dates to 2018, where the first dose of nusinersen, a gene therapy product for patients with spinal muscular atrophy, was administered at the East Jeddah Hospital in Saudi Arabia [30]; the drug is now approved in Kuwait, Qatar, and the United Arab Emirates (UAE) [31]. In 2019, voretigene neparvovec, a gene therapy treatment for inherited retinal blindness, was approved by the Ministry of Health and Prevention and the Saudi Food and Drug Authority in the UAE and Saudi Arabia, respectively [32, 33]. Another gene therapy product, onasemnogene abeparvovec, was used to treat children with spinal muscular atrophy in Egypt, Saudi Arabia, Kuwait, Qatar, and the UAE [34,35,36,37,38,39]. Outside of North America, the Hamad General Hospital in Qatar was the first to administer this drug. For cell therapy products, tisagenlecleucel, a chimeric antigen receptor T-cell therapy product, was approved by the Saudi Food and Drug Authority in 2022 [40]. This reflects the variability in resources and capacities across the MENA region. Indeed, according to the World Bank, the MENA region includes high-income (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, UAE) and low- and middle-income countries (Lebanon, Djibouti, Egypt, Iran, Iraq, Morocco, Tunisia, Jordan, Libya, Morocco, Syria, Tunisia, West Bank and Gaza, Yemen) [27].