Females Exhibit Stronger Immunity to AAV Vectors_Implications for Sex-Based Differences in Gene Therapy

 

In a landmark 2025 study published in Gene Therapy, a research team led by Dr. Ronit Mazor at the U.S. FDA’s Office of Gene Therapy, in collaboration with researchers from Pomega Corporation, uncovered a key factor influencing AAV gene therapy: biological sex (1). Their findings show that females mount stronger preexisting immune responses to AAV vectors than males, including higher antibody levels, greater neutralization capacity, and elevated inflammatory cytokine production. These results have major implications for the safety, effectiveness, and fairness of gene therapy, highlighting sex as a critical variable in vector design, patient selection, and regulatory strategy.

AAV Gene Therapy: A Transformative Approach

Adeno-associated virus (AAV)-based gene therapy represents a transformative approach for treating monogenic disorders, offering potential cures for diseases previously deemed untreatable. Engineered AAV vectors deliver functional copies of genes to target cells, demonstrating remarkable success across various therapeutic areas. The favorable safety profile of AAVs, characterized by their non-pathogenic nature and low integration frequency, combined with their ability to transduce both dividing and non-dividing cells across various tissues (liver, muscle, CNS, retina) has established them as the leading platform for in vivo gene therapy.

The clinical success of this field is evidenced by the growing number of FDA-approved therapies. Zolgensma (onasemnogene abeparvovec-xioi, AAV9) for spinal muscular atrophy was the first systemically administered AAV vector approved by the FDA in 2019. This was followed by Luxturna (voretigene neparvovec-rzyl), AAV2) for inherited retinal dystrophy, Elevidys (delandistrogene moxeparvovec-rokl, AAVrh74) for Duchenne muscular dystrophy, Hemgenix (etranacogene dezaparvovec-drlb, AAV5) and Beqvez (fidanacogene elaparvovec, AAVSpark100) for hemophilia B, and Roctavian (valoctocogene roxaparvovec, AAV5) for hemophilia A. More recently, Upstaza (eladocagene exuparvovec, AAV2) was approved for aromatic L-amino acid decarboxylase deficiency. These approvals mark significant milestones in translating gene therapy from experimental concept to clinical reality.

Beyond these approved therapies, the AAV gene therapy pipeline is expanding rapidly. According to recent industry analyses, over 300 AAV-based gene therapies are currently in various stages of development, with approximately 50% in clinical trials. These investigational therapies target a diverse range of conditions including neurological disorders, cardiovascular diseases, ophthalmic conditions, and metabolic diseases.

Current estimates indicate that there are more than 700 AAV-based gene therapy programs in various stages of development worldwide (2).  Regarding their clinical progression, detailed industry analyses and clinical trial databases report that over 100 AAV-based therapies are currently in clinical trials, with figures such as 176 clinical trials registered as of June 2025 and another source presenting a summary of 238 rAAV-based gene therapy clinical trials (3.4).

The Challenge of Preexisting Immunity in AAV Gene Therapy

Despite the remarkable progress in AAV gene therapy development, a significant hurdle persists: preexisting humoral immunity against the AAV capsid. Natural exposure to wild-type AAVs is common, with studies indicating that 30-70% of the population has preexisting antibodies against common AAV serotypes. These circulating antibodies can neutralize therapeutic vectors, impair transduction efficiency, reduce therapeutic efficacy, and potentially contribute to immune-mediated toxicities.

Immune responses, both humoral (antibody-mediated) and cellular, can rapidly clear AAV vectors, compromise transgene expression, and precipitate adverse reactions, including complement activation and thrombotic microangiopathies. The presence of preexisting neutralizing antibodies (NAbs) to AAV capsids has become a major consideration in clinical trial design, often leading to the exclusion of seropositive individuals from trials or the implementation of risk mitigation strategies such as plasmapheresis or immunosuppressive regimens.

Understanding factors influencing this preexisting immunity is crucial for optimizing trial design, patient selection, and vector engineering. While sex is a well-established modulator of immune responses to pathogens and vaccines, females generally mount stronger humoral and cellular responses and are more susceptible to autoimmune diseases, its specific impact on AAV immunity had remained largely unexplored prior to recent studies. This gap is particularly relevant as gene therapies expand beyond predominantly male conditions (e.g., X-linked hemophilias, Duchenne muscular dystrophy) to diseases affecting both sexes equally or predominantly females, such as Rett syndrome.

Study Design and Methodological Approaches

The comprehensive investigation into sex-based differences in AAV immunity employed rigorous methodological approaches across multiple dimensions. The study utilized two independent serum cohorts recruited across the United States: Cohort 1 from the NIH Blood Bank in Bethesda, Maryland (n=120), and Cohort 2 from BioIVT, spanning multiple sites in Florida, Tennessee, and Pennsylvania (n=160). This geographical diversity helped mitigate potential regional bias and strengthens the generalizability of the findings.

The researchers implemented quantitative assays to assess various aspects of immune response against five natural AAV serotypes (AAV1, AAV2, AAV5, AAV8, and AAV9). These included ELISA-based binding titers measured using both a “signal-to-noise” (ΔO.D.) approach and traditional titer calculation (interpolating dilution yielding a specific ΔO.D.). The study also conducted neutralization assays using a NanoLuc-AAV9 system to measure NC50 values (serum dilution resulting in 50% neutralization) on HEK293 cells, providing a functional assessment of antibody activity.

To characterize the humoral response in greater detail, the researchers performed immunoglobulin subclass and isotype profiling, including IgG1-4, IgM, and IgA. This analysis revealed not only quantitative differences but also qualitative distinctions in the immune response between sexes. The technical strengths of the study included the use of side-by-side sham controls, Benzonase treatment to remove contaminating DNA, iodixanol gradient purification, and ELISA quantification of vector particles rather than genome copies to minimize empty-capsid artifacts.

Beyond humoral immunity, the investigators extended their analysis to cellular immune responses by stimulating peripheral blood mononuclear cells (PBMCs) from male and female donors with AAV9. Following stimulation, they performed high-plex secretome profiling to quantify cytokine and chemokine secretion, providing insights into the innate immune response to AAV vectors. Flow cytometry was employed to identify the cellular sources of these differential responses, revealing that the cytokine-producing cells were largely CD19- and CD3-negative, suggesting monocytes, dendritic cells, or natural killer cells as the primary contributors.

Sex Differences in Preexisting Antibody Levels

The core finding across the studies is the consistently higher levels of preexisting binding antibodies against multiple AAV serotypes in female sera compared to males. This sex-based disparity was robustly demonstrated using distinct quantitative methods across two independent cohorts, strengthening the validity of the observation.

In Cohort 1, females who were seropositive for AAV9 exhibited a mean titer of 611 versus 434 in males, while in Cohort 2, the difference was 334 versus 252. The signal-to-noise analysis corroborated these results, showing higher ΔO.D values in female samples (1.0 vs 0.64 in Cohort 1; 0.69 vs 0.55 in Cohort 2). Importantly, the percentage of seronegative individuals was similar in both sexes, indicating comparable exposure rates to AAVs, but the magnitude of the immune response was consistently greater among females.

This pattern extended beyond AAV9 to other serotypes commonly used in gene therapy. Analysis across AAV1, AAV5, and AAV8 revealed that females also mounted consistently greater antibody responses than males for these serotypes. The effect size, while modest (1.2-1.5-fold higher geometric mean binding titers in females), carries clinical significance because many clinical vector exclusion thresholds are set at specific titer levels (often ≥ 1:100). Modeling the published titre distributions predicts approximately 10% additional disqualification of women for systemic AAV9 trials, representing a meaningful impact on patient eligibility.

Interestingly, no significant sex differences were observed for AAV2, which showed comparable antibody levels between sexes. The authors suggest this exception may be due to a higher frequency of AAV2-seronegative women, corroborating earlier population studies. This serotype-specific variation suggests that the antigenic determinants recognized by the immune system may differ between serotypes, potentially due to variations in capsid protein structure and epitope presentation.

The studies effectively addressed potential confounders like age (no correlation found) and used appropriate statistical tests (Mann-Whitney U test, ANOVA). The use of sham controls and background subtraction minimized non-specific binding artifacts, while the inclusion of multiple serotypes demonstrated that the effect is not serotype-specific, though its magnitude varies.

Immunoglobulin Subclass Patterns

Beyond total IgG levels, the studies revealed fundamental differences in the composition of the AAV-specific antibody response between sexes. IgG1 was the dominant subclass in both sexes, aligning with known immune responses to viral antigens and representing approximately 60% of the total response. This consistency suggests a Th2-biased recall response to capsid antigens in both males and females.

However, the secondary dominant subclass differed significantly between sexes, with important immunological implications. Females exhibited significantly higher levels of IgA, while males showed higher levels of IgG2. This finding is biologically significant as different antibody subclasses activate distinct immune effector mechanisms. The predominance of IgA in females is particularly noteworthy, as IgA plays a crucial role in mucosal immunity and neutralization at epithelial surfaces. Previous research in primates has shown that higher IgA titers against simian immunodeficiency virus (SIV) correlated with enhanced viral clearance in females, suggesting that the higher IgA levels against AAV in females might contribute to more efficient vector neutralization.

Conversely, the higher IgG2 levels observed in males may have different functional consequences. IgG2 subclass switching is androgen-regulated, providing a plausible mechanistic link to the observed sex difference. IgG2 is often linked to responses against polysaccharide antigens but is generally less effective at complement activation and Fc-receptor binding than IgG1 or IgG3. This suggests that the male immune response to AAV may be less effective at certain effector functions compared to the female response.

The distinct antibody subclass profiles (IgG1/IgA dominant in females versus IgG1/IgG2 in males) indicate that the sex-based differences in AAV immunity are not merely quantitative but involve qualitative differences in the immune response. These differences in immunoglobulin subclass distribution may contribute to the observed variations in neutralizing capacity and have important implications for understanding the mechanisms underlying sex disparities in gene therapy outcomes.

Serotype-Specific Differences in Immune Responses

The investigation of immune responses across multiple AAV serotypes revealed important serotype-specific patterns in sex-based immunity. While females showed higher antibody levels against AAV5, AAV8, and AAV9, no significant sex differences were observed for AAV2. This finding has significant practical implications for gene therapy development and vector selection strategies.

The reasons for this serotype-specific discrepancy remain unclear but may relate to differences in natural exposure patterns or capsid epitope immunogenicity. The AAV capsid proteins vary between serotypes, with differences in surface-exposed loops and domains that could influence antigen recognition and immune response. The observation that AAV2 shows less pronounced sex differences suggests that its antigenic determinants may be recognized differently by the immune system compared to other serotypes.

These findings suggest that gene therapies using serotypes such as AAV5 or AAV8 may face greater immune barriers in female patients. The implication is twofold: first, there may be a sex-based bias in patient eligibility depending on the serotype used; second, capsid engineering efforts must consider sex-based immunogenicity profiles when developing next-generation vectors.

The analysis also revealed high cross-reactivity among serotypes, with most individuals showing binding to multiple serotypes. This cross-reactivity complicates the strategy of switching serotypes to circumvent preexisting immunity, as antibodies against one serotype may still neutralize related serotypes to some degree. However, the serotype-specific nature of the sex-based differences suggests that AAV1 and AAV2 might be more suitable for gene therapies targeting primarily female populations, as they would face less preexisting immunity. Conversely, AAV5, AAV8, and AAV9 might present greater challenges in female patients due to higher preexisting antibody levels.

The authors also suggest that engineered AAV vectors with lower homology to natural serotypes might be more effective for female patients, a hypothesis that warrants further investigation. As the field moves toward developing novel capsids with enhanced tropism and reduced immunogenicity, considering sex-based differences in preexisting immunity will be crucial for ensuring equitable access to gene therapies across patient populations.

Functional Neutralization Capacity

The functional consequence of higher binding titers was confirmed through rigorous neutralization assays (NAb), which revealed that female sera exhibited significantly stronger inhibition of AAV9 transduction. The dilution required to achieve 50% neutralization (NC50) was significantly higher in females compared to males, directly correlating with the higher binding titers. This finding demonstrates that the quantitative differences in antibody levels translate into meaningful functional differences in the ability to neutralize AAV vectors.

The correlation between binding titers and neutralizing titers was moderate to high (R²=0.83 in Cohort 1, R²=0.65 in Cohort 2), with approximately 73% of samples being positive for both binding and neutralization antibodies. However, 20-35% of samples with binding antibodies lacked detectable neutralizing activity, highlighting that not all binding antibodies are functionally neutralizing. This distinction is crucial for clinical applications, as neutralizing antibodies pose a greater barrier to successful gene therapy than non-neutralizing binding antibodies.

Intriguingly, even when matched for binding titer level (low/medium/high), female sera tended to show stronger neutralization at higher dilutions, suggesting qualitative differences beyond mere quantity. These qualitative differences may involve antibody affinity, epitope specificity, or other functional characteristics influenced by the distinct immunoglobulin subclass profiles observed between sexes. The female profile (high IgG1 + IgA) may inherently be more potent or prone to specific effector functions contributing to neutralization or immune complex formation.

The Nab assay design using a luciferase reporter provides a sensitive and quantitative functional readout. The correlation with binding titers validates the main finding, while the observed discordance and the subtle qualitative difference in neutralization efficiency between sexes with matched titers point towards the complexity of humoral immunity and the importance of the antibody characteristics revealed by the subclass analysis.

These findings have profound implications for clinical practice. Many current trials exclude patients with neutralizing antibody titers above a predefined threshold (often 1:5 or 1:10). The data suggest that more women will fail both gates, necessitating plasmapheresis or capsid-escape strategies. For trials or approved products that do not exclude based on preexisting antibodies, the higher neutralization titers in females could lead to suboptimal transduction, lower transgene expression, and reduced clinical efficacy compared to males, particularly in individuals with medium/high titers.

Cellular Immune Response Differences

Moving beyond humoral immunity, the studies investigated innate and early inflammatory responses at the cellular level using ex vivo stimulation of human PBMCs with AAV9. Female PBMCs exhibited a more robust cytokine and chemokine response than male PBMCs, indicating enhanced innate immune activation. This was particularly evident at the higher vector dose (1×10¹¹ particles/ml), where females showed significantly higher relative secretion of IL-6 and GM-CSF compared to unstimulated controls than males.

Chemokines crucial for immune cell recruitment were also differentially regulated between sexes. CCL5/RANTES, CCL7/MCP-3, CXCL10, and CXCL9 were significantly more upregulated in females in a dose-dependent manner. IL-1β showed strong induction in both sexes, but with a trend toward higher levels in females. These cytokines and chemokines are associated with antigen-presenting cell activation, T cell recruitment, and inflammatory amplification—hallmarks of an immune microenvironment that could accelerate vector clearance and hinder therapeutic efficacy.

Flow cytometry suggested that the differential IL-6 secretion originated primarily from non-B/non-T cells (e.g., monocytes, dendritic cells), not directly from antibody-secreting B cells. No significant sex difference was found in the activation of a specific antigen-secreting B cell subset (CD3-CD19+CD24-CD27+CD38+). This finding suggests that the sex-based differences in cellular immune responses involve fundamental differences in innate immune signaling pathways rather than adaptive B cell responses.

The pronounced increase in IL-6 secretion by female PBMCs is particularly significant, as IL-6 is a key pro-inflammatory cytokine involved in B cell differentiation and antibody production. This finding suggests that the enhanced humoral response in females may be driven by a more robust inflammatory response at the cellular level. Furthermore, IL-6 fold-change correlated with anti-capsid titre (Spearman r = 0.64), suggesting positive feedback between innate activation and humoral memory.

The differential secretion of chemokines involved in immune cell recruitment and activation further supports the notion of a fundamentally different immune response to AAV between sexes. These findings provide a plausible cellular mechanism underpinning the humoral differences observed. The stronger inflammatory response (IL-6, chemokines) in females could create a more immunogenic microenvironment upon vector administration, potentially contributing to faster vector clearance, enhanced adaptive immune responses (including antibody production), and potentially an increased risk of inflammation-related adverse events.

Implications for Patient Eligibility and Clinical Trial Design

The discovery of significant sex-based differences in preexisting immunity to AAV vectors has profound implications for patient eligibility and clinical trial design. Many current trials exclude patients with neutralizing antibody titers above a predefined threshold (often 1:5 or 1:10). The studies suggest that adult females are significantly more likely to exceed these thresholds due to higher baseline immunity against prevalent serotypes like AAV9, AAV5, and AAV8.

This could systematically exclude a larger proportion of female patients from trials and, ultimately, from receiving approved therapies, exacerbating existing health disparities. As gene therapies expand to broader populations, including adult women and patients with female-prevalent disorders, addressing these immunological differences will be essential for maximizing therapeutic reach and ensuring equitable access.

The findings challenge the prevailing notion of uniform patient eligibility for gene therapy trials and signal a need for sex-specific clinical strategies. Trial protocols must begin stratifying enrollment and analysis by sex and report seroprevalence and titer data disaggregated by sex. Sponsors should pre-stratify enrolment plans and consider sex-adjusted titre thresholds to avoid inadvertent exclusion of women from trials.

Historically, many gene therapy trials have focused on X-linked disorders that primarily affect males (such as hemophilia) or have targeted very young patients with low sex hormone levels. As gene therapy applications expand to include conditions affecting both sexes or predominantly females, understanding sex-based differences in immune responses becomes increasingly critical. The enhanced antibody titers and neutralization in females may affect outcomes, both in terms of efficacy and potential immune-mediated toxicity, necessitating careful monitoring in ongoing and future trials.

Impact on Therapeutic Efficacy and Safety

Beyond patient eligibility, the observed sex-based differences in preexisting immunity have significant implications for therapeutic efficacy and safety. For trials or approved products that do not exclude based on preexisting antibodies, the higher neutralization titers in females could lead to suboptimal transduction, lower transgene expression, and reduced clinical efficacy compared to males, particularly in individuals with medium/high titers.

The potential difference in therapeutic outcome based on sex needs careful monitoring in ongoing and future trials. Even when female patients with preexisting antibodies are included in trials, the higher neutralizing capacity of their antibodies might result in reduced transduction efficiency and therapeutic efficacy. This could manifest as sex-based differences in treatment outcomes that have not been previously recognized or accounted for in clinical trial design.

The enhanced inflammatory response observed in female PBMCs also raises questions about potential sex differences in acute immune reactions or delayed toxicities following AAV administration. While not directly tested in these studies, the stronger cytokine/chemokine response could theoretically contribute to a higher incidence or severity of immune-mediated adverse events (e.g., complement activation, hepatotoxicity) in females. Close sex-stratified safety monitoring is essential to identify and address any such differences.

The clinical significance of low to medium antibody titers remains an area of debate in the field, with conflicting evidence regarding their impact on transduction efficiency. The studies add another layer of complexity to this discussion by suggesting that the impact of a given titer may differ between sexes. This underscores the need for more nuanced approaches to assessing preexisting immunity and its impact on therapeutic outcomes.

Vector Selection and Engineering Considerations

The findings highlight the importance of serotype selection based on the target patient population. For diseases primarily affecting females (e.g., Rett syndrome), serotypes showing less pronounced sex differences in preexisting immunity (like AAV2 in these studies, though context matters) or engineered capsids with reduced cross-reactivity to common wild-type AAVs might be preferable.

The serotype-specific nature of the sex-based differences suggests that rational vector selection could partially mitigate eligibility biases, although this would need functional confirmation in clinical settings. AAV1 and AAV2 might be more suitable for gene therapies targeting primarily female populations, as they would face less preexisting immunity. Conversely, AAV5, AAV8, and AAV9 might present greater challenges in female patients due to higher preexisting antibody levels.

The development of capsids inherently less immunogenic or resistant to neutralization is crucial for advancing the field. Engineered AAV vectors with lower homology to natural serotypes (e.g., AAV-LK03, PHP.eB) may minimize female disqualification. As the field moves toward developing novel capsids with enhanced tropism and reduced immunogenicity, considering sex-based differences in preexisting immunity will be crucial for ensuring equitable access to gene therapies across patient populations.

The distinct antibody subclass profile (high IgA in females) and the stronger inflammatory response provide clues for further research into the biological underpinnings of sex differences in AAV immunity, potentially involving sex hormones, X-chromosome genes, or microbiome interactions. Understanding these mechanisms could inform the design of next-generation vectors that are less susceptible to sex-based differences in preexisting immunity.

Mitigation Strategies and Future Directions

Several strategies have been proposed to overcome preexisting immunity in AAV gene therapy, including plasmapheresis, immunosuppressive regimens, empty capsid decoys, and engineered Fc-silenced antibodies. The discovery of significant sex-based differences in preexisting immunity suggests that these strategies may need optimization or different application thresholds considering the sex-based differences in titer levels and potentially immune reactivity.

Short courses of rituximab + sirolimus or plasmapheresis could be more frequently required in women, adding cost and risk to treatment protocols. The development of sex-specific mitigation strategies could help ensure more equitable access to gene therapies across patient populations.

Future research should focus on several key areas. Larger, prospective studies correlating pre-treatment sex-specific immunity with clinical outcomes (transduction efficiency, transgene expression, efficacy, safety) in AAV gene therapy trials are needed to establish the clinical relevance of the observed immunological differences. Mechanistic studies exploring the drivers of higher IgA and stronger inflammatory responses in females could provide insights into the biological basis of these differences and inform the development of targeted interventions.

Investigating sex differences in T-cell responses to AAV capsid or transgene is another important area for future research, as cellular immune responses can also impact gene therapy outcomes. The role of sex hormones, genetic factors, and immune regulation in shaping these differences warrants further investigation.

From a regulatory perspective, the FDA’s recent draft guidance on neutralizing antibodies does not yet incorporate sex-specific thresholds. Regulatory agencies should consider these findings when developing guidelines for patient selection and eligibility criteria in gene therapy trials.

Conclusions and Perspectives

The comprehensive analysis of sex-based differences in preexisting immunity to AAV vectors reveals a significant and multifaceted sex bias in immunity against AAV vectors. Females exhibit higher preexisting antibody titers (particularly against AAV9, AAV5, and AAV8), a distinct antibody subclass profile (IgG1/IgA dominant), enhanced neutralizing capacity, and a stronger inflammatory cellular response compared to males. This bias is not merely quantitative but involves qualitative differences in the immune response.

These findings necessitate a paradigm shift in AAV gene therapy development and clinical practice. Ignoring sex as a critical biological variable risks excluding female patients from potentially curative treatments, misinterpreting clinical trial data, and overlooking potential differences in safety and efficacy. Integrating sex-stratified analysis into all stages of gene therapy research, from preclinical vector design to clinical trial enrollment, monitoring, and data interpretation, is essential for ensuring equitable access and optimizing outcomes for all patients.

As the AAV gene therapy pipeline continues to expand, rigorous exploration of sex-based and other demographic immune biases will be essential for advancing both the science and equity of gene therapy. The studies underscore that achieving the full potential of gene therapy requires a nuanced understanding of host factors, with patient sex being a fundamental determinant of immune engagement with AAV vectors.

References

  1. Unveiling the sex bias: higher preexisting and neutralizing titers against AAV in females and implications for gene therapy. Gene Ther 2025; 32, 339–348; https://doi.org/10.1038/s41434-025-00528-7
  2. Advancing AAV production with high-throughput screening and transcriptomics. Cell & Gene Therapy Insights 2024; 10, 821–840; DOI: 10.18609/CGTI.2024.095 https://www.insights.bio/cell-and-gene-therapy-insights/journal/article/3254/advancing-aav-production-with-highthroughput-screening-and-transcriptomics
  3. Adeno-associated virus as a delivery vector for gene therapy of human diseases. Sig Transduct Target Ther 2024; 9;  https://doi.org/10.1038/s41392-024-01780-w
  4. Clinical and Translational Landscape of Viral Gene Therapies. Cells 2024; 13 (22), 1916; https://doi.org/10.3390/cells13221916

 

Disclaimer: This blog post is intended solely for educational and scientific informational purposes. Any mention of therapeutic drug names, including FDA-approved medications, is for the purpose of accurate reporting and discussion of biomedical research and does not constitute medical advice, endorsement, or promotion. Readers should not interpret the content as a recommendation for any specific treatment. Always consult a qualified healthcare professional for medical advice or treatment decisions.

 

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Our Recent Publication/Meeting Presentation on Gene Therapy

1. Development of VNX-101, an Adeno-Associated Virus with Less Immunogenicity and Efficient Long-Term Expression of a CD19 T-Cell Engager. Molecular Therapy Methods & Clinical Development, published online July 24, 2025.

2. Development of a Pharmacokinetic (PK) Mouse Serum GLP ELISA for an Anti–CD19–AntiCD3 Diabody
bioRxiv 2025.03.19.644217; doi: https://doi.org/10.1101/2025.03.19.644217.

3. Cell-Based Potency Assay for Anti-CD3-Anti-CD19 Diabody. bioRxiv 2025.04.15.648836v1 https://www.biorxiv.org/content/10.1101/2025.04.15.648836v1.

4.  American Society of Hematology (ASH) Annual Meeting 2024.
Abstract link: Using Gene Therapy to Solve Challenges with CAR-T Cell Immunotherapy: Lead Selection and Preclinical Development of an Adeno-Associated Virus with Reduced Immunogenicity  Exhibiting Efficient and Long-Term Expression of an Anti-CD19 T-Cell Engager.

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