Patient and public perspectives on cell and gene therapies: a systematic review

The study investigates how patients and the public understand and perceive cell and gene therapies, including their knowledge levels, acceptance, perceived risks and benefits, and information needs. The context is that cell and gene therapies have transformative potential for restoring function and curing disease, but raise significant logistical, economic, ethical, and social challenges. The purpose is to systematically review existing evidence on patient and public perspectives to inform future research, education, and awareness activities. Understanding these perspectives is important because they can influence clinical trial participation, regulatory and funding decisions, and the eventual uptake and implementation of these therapies in health systems.

The review situates current patient and public perspectives within broader debates on stem cell and gene therapy ethics, media influence, and policy trends. Prior work indicates variable public acceptance, often shaped by concerns about embryonic stem cell use (perceived as morally problematic and “playing God”), and caution about gene editing for enhancement. Media coverage has historically been sensational, focusing on breakthroughs or safety incidents, with online sources often omitting risk evidence, potentially fueling therapeutic misestimation. Polls from organizations such as STAT-Harvard and Pew Research Center show consistent public skepticism toward germline editing for enhancement but some support for therapeutic applications and federal funding, and higher trust in scientists and physicians compared to politicians or the media. Comparisons to oncology research suggest similar therapeutic misconception patterns (e.g., overestimation of benefits in early-phase trials). Overall, the existing literature underscores persistent knowledge gaps, ethical concerns, the influence of information sources, and the importance of trustworthy, balanced communication.

Design and registration: Systematic review registered with PROSPERO (CRD42019138131) and reported according to PRISMA.

Search strategy: Adapted the Scottish Intercollegiate Guidelines Network (SIGN) patient issues filter. No language or study design restrictions. Databases searched included Medicine, Embase, CINAHL, PsycINFO, Cochrane Database of Systematic Reviews, DARE, and the Cochrane Central Register of Controlled Trials; Current Controlled Trials and PROSPERO were searched for ongoing studies, reviews, and grey literature. Searches were conducted between December 2018 and 5 April 2019, focusing on studies published from 1 January 2005 onward, with contextual rationale noting key EU ATMP regulatory milestones (2008–2009) and the first successful EU phase III gene therapy trial in 2009.

Eligibility criteria: Included qualitative and/or quantitative studies focusing on cell and gene therapies in clinical application or under consideration within clinical trials; involving patients who have received or may be eligible for cell/gene therapy, family carers, or members of the general public; and exploring/evaluating knowledge, understanding, expectations, or perceptions of cell/gene therapy. Excluded narrative reviews, commentaries, opinion pieces, and letters without primary findings; studies restricted to healthcare professionals/scientists; studies focused entirely on embryonic stem-cell therapy or germline therapy; and studies on hematopoietic stem-cell transplants.

Selection process: Records exported to EndNote. One reviewer (K.M.) screened all titles/abstracts; a second reviewer (O.L.A.) independently screened 20% for consistency. Potentially eligible full texts were assessed independently by the same reviewers, with discrepancies resolved by discussion. Reference lists and citations of included studies were hand-searched.

Data extraction: A piloted extraction form captured participant group and demographics where available; sample size; health status; therapy type; standard of care; setting; study design; study quality; and author conclusions. Extracted by K.M., O.L.A., L.E., and C.M., with cross-checking for accuracy and consistency.

Critical appraisal: No formal unified checklist due to methodological heterogeneity. Instead, studies were appraised on five indicators: response rate, sample size, participant characteristics, study methods, and funding/competing interests.

Synthesis: Due to heterogeneity, no meta-analysis or qualitative meta-synthesis was performed. A narrative synthesis (Popay et al.) was undertaken, including descriptive summaries, exploration of associations within and across studies, and discussion of implications and recommendations.

Screening yield: 10,735 titles/abstracts screened; 151 full texts evaluated; 35 publications included.

• Themes: Four overarching themes emerged: (1) Knowledge and understanding of cell and gene therapies; (2) Acceptance of cell and gene therapies; (3) Understanding of risks and benefits; and (4) Information needs and sources.
• Knowledge: Patients with conditions such as ischaemic stroke, cystic fibrosis, and sickle cell anemia typically reported limited prior knowledge. Some groups (e.g., certain young adults) showed higher awareness of gene therapy. Male gender and higher educational attainment were associated with greater knowledge. Patients were often unclear about cell sources, viral vectors and infection risk, chemotherapy use, and distinctions between research trials and licensed clinical applications. Therapeutic misconception (confusing research goals with clinical care) was common.
• Acceptance: Acceptance varied but generally increased after provision of information. Greater acceptance was associated with male gender, older age, higher education, longer disease duration and severity, and greater perceived risk of death. Some older patients reported altruistic motivations to participate in trials. In one study, 67% considered a reasonable therapy price to be under US$1,000, despite contemporaneous estimates ranging from US$5,000 to US$39,500.
• Risks and benefits: Many patients overestimated benefits (therapeutic misestimation), showed eagerness for access, minimized side effects, and had unrealistic timelines. Others were concerned about uncertain benefit-risk, especially parents of younger children, though risk tolerance increased as children aged or illness worsened and options narrowed. Concerns about chemotherapy were notable, including fear of cancer risks and taxing side effects.
• Ethics and beliefs: Public acceptance showed geographical variation and was generally lower for uses involving embryonic cells, with perceptions of moral boundary-crossing. Gene editing for enhancement drew low support overall, though some populations showed neutral to supportive views for selected enhancements; religion’s influence was inconclusive. Concerns included long-term impacts on genetic diversity.
• Information needs and sources: Patients consistently wanted more, clearer, and personalized information, including data from large, long-term studies, explicit risks/side effects, and study eligibility criteria. Television, newspapers/magazines, clinicians, friends, and colleagues were cited as information sources. Physicians were viewed as most trustworthy, yet patients did not always discuss interests/concerns with them. Trust in scientists, medical researchers, and ethics review processes was higher than in media, religious leaders, or political systems; some regional distrust of regulators was noted. Media reports often emphasized breakthroughs/safety incidents and sometimes omitted discussion of evidence strength and risks.
• Critical appraisal snapshot: Only 10 publications (approximately 40% of a subset) reported response rates. Sample sizes varied; rare disease studies faced recruitment challenges. Some recruitment via patient advocacy groups raised potential selection bias. Funding sources were reported by about 83% of publications, mostly non-pharmaceutical; funder influence on interpretation could not be fully assessed. Overall, acceptance and perceptions were closely tied to knowledge levels, perceived benefits/risks, ethical/moral beliefs, and the trustworthiness of information sources.

The review addresses the core question by demonstrating that patient and public acceptance of cell and gene therapies is strongly influenced by their knowledge, understanding of risks and benefits, ethical/moral beliefs, and trust in information sources. Providing clear, balanced information tends to increase acceptance and can correct therapeutic misconceptions and misestimation. The findings underscore the central role of physicians and scientists as trusted communicators, while highlighting the risk that sensational or unbalanced media coverage can distort expectations and undermine informed decision-making. Comparisons to oncology trials suggest a broader pattern of overestimating benefits in early-phase research, implying a need for better communication about trial purposes, phases, and realistic outcomes. Ethical debates (e.g., embryonic cell use, gene editing for enhancement) remain salient in shaping public opinion and policy preferences, with implications for funding, regulation, and equitable access. The review posits a hypothetical model in which acceptance is driven by knowledge and risk-benefit understanding, which are, in turn, shaped by information sources and their perceived trustworthiness. For health systems, these insights imply that uptake of cell and gene therapies will depend not only on clinical and cost-effectiveness evidence but also on addressing information needs, building trust, engaging patients and carers, and acknowledging ethical concerns. Tailored educational strategies for different audiences (patients versus general public) and proactive involvement of clinicians and scientists in communication are recommended.

This systematic review consolidates evidence that patient and public perspectives on cell and gene therapies are shaped by knowledge, risk-benefit understanding, ethical beliefs, and trust in information sources. Acceptance generally increases with clear, balanced information, underscoring the need for targeted education and engagement. The review highlights substantial knowledge gaps, therapeutic misconceptions, and concerns about chemotherapy, ethics, costs, and access. It calls for high-quality studies to explore patient and public opinions and real-world experiences, and emphasizes the importance of involving patients and public contributors in co-designing research and educational resources. Future research directions include: (1) studies capturing experiences of recipients of cell and gene therapies; (2) investigations of patient views on reimbursement, prioritization, and geographic access; (3) evaluation of social and traditional media’s role in information provision and strategies to enhance trustworthiness; (4) use of consensus methods (e.g., Delphi, nominal group technique) to set priorities for education and communication; and (5) application of health economic preference methods (e.g., discrete choice experiments) to understand trade-offs and societal values.

• Heterogeneity of included studies (methods, populations, therapies) precluded meta-analysis and limited comparability.
• Variable and sometimes limited reporting quality: incomplete reporting of response rates (~40% in a subset), participant characteristics, and methods; rare disease studies limited detail to protect anonymity.
• Potential recruitment bias where participants were accessed via advocacy groups.
• Risk of framing effects and limited validity in survey-based studies with closed-ended questions; differences in how questions were posed across studies.
• Uncertain influence of information provided during consent or study participation on respondents’ views, as the extent and content of pre-study information were unclear.
• Fewer studies on gene therapy relative to cell therapy, potentially limiting representativeness of gene therapy perspectives.
• Incomplete clarity on funder roles in interpretation in some studies, introducing potential bias.
• Generalizability may be constrained by small samples, especially in rare diseases, and by geographical and cultural variation.