Patients with preexisting anti-adeno-associated virus serotype 8 (AAV8) neutralizing antibodies (NAbs) are currently excluded from AAV8 gene therapy trials. Therefore, the assessment of biologically relevant AAV8-NAb titers is critical for product development in gene therapy. However, standardized assays have not been routinely used to determine anti-AAV8-NAb titers, contributing to a wide range of reported anti-AAV8 prevalence rates. Using a clinical in vitro NAb assay in a separate study, a higher than expected anti-AAV8-NAb prevalence of about 50% was found in international cohorts. This comparative study has a translational character, confirming the biological relevance of anti-AAV8-antibody titers measured by this assay. The significance of low-titer anti-AAV8 NAbs is shown, along with the relevance of the in vitro assay cutoff (1:5) compared with other assays. Importantly, internally standardized reagents and purified AAV8 constructs containing 90% full capsids were used to reduce the effect of empty capsids. It was found that even very low anti-AAV8-NAb titers (<1:5) could efficiently hinder transduction in vivo, demonstrating the importance of sensitive NAb assays for clinical applications. The in vitro NAb assay was found to be more sensitive than an in vivo NAb assay and thus more suitable for patient screening. Additionally, the study showed that anti-AAV8-NAb titers <1:5 were very rare, further supporting the in vitro assay. However, assays using a lower cutoff may still be useful to explain potential variances in transgene expression. These findings support the relevance of the higher than expected prevalence of anti-AAV8 NAbs, highlighting the need for strategies to circumvent preexisting anti-AAV8 NAbs.

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The fast evolution in computational and sensor technologies brings previously niche solutions to a wider userbase. As such, 3D reconstruction technologies are reaching new use-cases in scientific and everyday areas where they were not present before. Cost-effective and easy-to-use solutions include camera-based 3D scanning techniques, such as photogrammetry. This paper provides an overview of the available solutions and discusses in detail the depth-image based Real-time Appearance-based Mapping (RTAB-Map) technique as well as a smartphone-based solution that utilises ARCore, the Augmented Reality (AR) framework of Google. To qualitatively compare the two 3D reconstruction technologies, a simple length measurement-based method was applied with a purpose-designed reference object. The captured data were then analysed by a processing algorithm. In addition to the experimental results, specific case studies are briefly discussed, evaluating the applicability based on the capabilities of the technologies. As such, the paper presents the use-case of interior surveying in an automated laboratory as well as an example for using the discussed techniques for landmark surveying. The major findings are that point clouds created with these technologies provide a direction- and shape-accurate model, but those contain mesh continuity errors, and the estimated scale factor has a large standard deviation.

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The Laboratory Automation Plug & Play (LAPP) framework is a high-level abstraction layer that makes the autonomous operation of life science laboratory robots possible. The plug & play nature lies in the fact that the manual teaching and configuration of robots is not required. A digital twin (DT) based concept is proposed that outlines the types of information that has to be provided for each relevant component of the system. In particular, for the devices that the robot interfaces with, the robot positions have to be defined beforehand in a device-attached coordinate system (CS) by the vendor. This CS has to be detectable by the vision system of the robot by means of optical markers placed on the front side of the device. With that, the robot is capable of tending the machine by performing the pick-and-place type transportation of standard sample carriers. This basic use case is the primary scope of the LAPP-DT framework. The hardware scope is limited to simple benchtop and mobile manipulators with parallel grippers at this stage. This paper first provides an overview of relevant literature and state-of-the-art solutions, after which it outlines the framework on the conceptual level, followed by the specification of the relevant DT parameters for the robot, for the devices and for the facility. Finally, appropriate technologies and strategies are identified for the implementation.