Anti-AAV Antibodies in AAV Gene Therapy: Current Challenges and Possible Solutions.
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ABSTRACT:
SUBMITTER: Weber T
PROVIDER: S-EPMC8010240 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Adeno-associated virus (AAV)-based vectors are promising tools for gene therapeutic applications, in part because AAVs are nonpathogenic viruses, and vectors derived from them can drive long-term transgene expression without integration of the vector DNA into the host genome. AAVs are not strongly immunogenic, but they can, nonetheless, give rise to both a cellular and humoral immune response. As a result, a significant fraction of potential patients for AAV-based gene therapy harbors pre-existing antibodies against AAV. Because even very low levels of antibodies can prevent successful transduction, antecedent anti-AAV antibodies pose a serious obstacle to the universal application of AAV gene therapy. In this review, we discuss the current knowledge of the role of anti-AAV antibodies in AAV-based gene therapy with a particular emphasis on approaches to overcome the hurdle that they pose.
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Project description:Brain-Computer Interface (BCI), in essence, aims at controlling different assistive devices through the utilization of brain waves. It is worth noting that the application of BCI is not limited to medical applications, and hence, the research in this field has gained due attention. Moreover, the significant number of related publications over the past two decades further indicates the consistent improvements and breakthroughs that have been made in this particular field. Nonetheless, it is also worth mentioning that with these improvements, new challenges are constantly discovered. This article provides a comprehensive review of the state-of-the-art of a complete BCI system. First, a brief overview of electroencephalogram (EEG)-based BCI systems is given. Secondly, a considerable number of popular BCI applications are reviewed in terms of electrophysiological control signals, feature extraction, classification algorithms, and performance evaluation metrics. Finally, the challenges to the recent BCI systems are discussed, and possible solutions to mitigate the issues are recommended.
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Project description:Hepatitis B virus (HBV) has afflicted humankind for decades and there is still no treatment that can clear the infection. The development of recombinant adeno-associated virus (rAAV)-based gene therapy for HBV infection has become important in recent years and research has made exciting leaps. Initial studies, mainly using mouse models, showed that rAAVs are non-toxic and induce minimal immune responses. However, several later studies demonstrated rAAV toxicity, which is inextricably associated with immunogenicity. This is a major setback for the progression of rAAV-based therapies toward clinical application. Research aimed at understanding the mechanisms behind rAAV immunity and toxicity has contributed significantly to the inception of approaches to overcoming these challenges. The target tissue, the features of the vector, and the vector dose are some of the determinants of AAV toxicity, with the latter being associated with the most severe adverse events. This review discusses our current understanding of rAAV immunogenicity, toxicity, and approaches to overcoming these hurdles. How this information and current knowledge about HBV biology and immunity can be harnessed in the efforts to design safe and effective anti-HBV rAAVs is discussed.
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Project description:BackgroundPatients perceive effective patient-doctor communication as an important metric when evaluating their satisfaction with health systems. Hence, optimal patient-physician communication is fundamental for quality healthcare. High-income countries (HICs) have extensively studied patient-resident communication. However, there is a dearth of similar studies in low- and middle-income countries (LMICs). Therefore, we aimed to explore the current state of and barriers to practicing good patient-resident communication and explore possible solutions to mitigate these challenges at one of the largest Academic Medical Centers in an LMIC.MethodsThis study employed an exploratory qualitative study design and was conducted at the Aga Khan University Hospital in Pakistan. Through purposive maximum variation sampling, 60 healthcare workers from diverse cohorts, including attendings, fellows, residents, and medical students, participated in eight focus group discussions.ResultsWe identified three key themes from the data: Status-quo of residents' communication skills and learning (Poor verbal and non-verbal communication, inadequate training programs, and variable sources of learning), Barriers to effective communication (Institutional barriers such as lack of designated counselling spaces, lack of resident insight regarding effective communication and deficits in intra-team communication), and the need for developing a communication skills curriculum (Design, implementation and scaling to other cohorts of healthcare workers).ConclusionsFindings from this study show that multifaceted factors are responsible for inadequate patient resident-physician communication, highlighting the need for and importance of developing a formal communication skills training curriculum for residents. These insights can be used to create standardized training for equipping residents with adequate skills for effectively communicating with patients which can improve healthcare service delivery and patient outcomes.
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Project description:HIV-1 causes AIDS, a syndrome that affects millions of people globally. Existing HAART is efficient in slowing down disease progression but cannot eradicate the virus. Furthermore the severity of the side effects and the emergence of drug-resistant mutants call for better therapy. Gene therapy serves as an attractive alternative as it reconstitutes the immune system with HIV-resistant cells and could thereby provide a potential cure. The feasibility of this approach was first demonstrated with the 'Berlin patient', who was functionally cured from HIV/AIDS with undetectable HIV-1 viral load after transplantation of bone marrow harboring a naturally occurring CCR5 mutation that blocks viral entry. Here, we give an overview of the current status of HIV gene therapy and remaining challenges and obstacles.
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Project description:Purpose of Review:The purpose of this review is to raise awareness, examine the challenges faced by wound care researchers and explore opportunities for potential improvements. Recent findings:Chronic wounds are associated with significant morbidity and mortality, and they represent a major medical and financial burden. Despite this, no new therapy has received FDA efficacy approval for the treatment of chronic wounds since 1997. Previous preclinical studies using animal models did not translate to human wounds due to inherent limitations of experimental models, variability in assessment methods and overall experimental design. Clinical trials continued to be challenged by the balance of the inclusion and exclusion criteria, the high cost and time expenditure of the trials, and the constraint of a single FDA-acceptable outcome of complete wound closure. Summary:Wound research faces multiple challenges in both pre-clinical and clinical research that slowed progress and development of efficacious therapies. Solutions to such challenges will provide new opportunities for improved study design in the future.
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Project description:ObjectiveThe UK Biobank provides a rich collection of longitudinal clinical data coming from different healthcare providers and sources in England, Wales, and Scotland. Although extremely valuable and available to a wide research community, the heterogeneous dataset contains inconsistent medical terminology that is either aligned to several ontologies within the same category or unprocessed. To make these data useful to a research community, data cleaning, curation, and standardization are needed. Significant efforts to perform data reformatting, mapping to any selected ontologies (such as SNOMED-CT) and harmonization are required from any data user to integrate UK Biobank hospital inpatient and self-reported data, data from various registers with primary care (GP) data. The integrated clinical data would provide a more comprehensive picture of one's medical history.Materials and methodsWe evaluated several approaches to map GP clinical Read codes to International Classification of Diseases (ICD) and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) terminologies. The results were compared, mapping inconsistencies were flagged, a quality category was assigned to each mapping to evaluate overall mapping quality.ResultsWe propose a curation and data integration pipeline for harmonizing diagnosis. We also report challenges identified in mapping Read codes from UK Biobank GP tables to ICD and SNOMED CT.Discussion and conclusionSome of the challenges-the lack of precise one-to-one mapping between ontologies or the need for additional ontology to fully map terms-are general reflecting trade-offs to be made at different steps. Other challenges are due to automatic mapping and can be overcome by leveraging existing mappings, supplemented with automated and manual curation.
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