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We report here the development of two different sensing strategies based on the use of antigen-conjugated nucleic acid strands for the detection of a bispecific antibody against the tumor-related proteins Mucin1 and epidermal growth factor receptor. Both approaches work well in serum samples (nanomolar sensitivity), show high specificity against the two monospecific antibodies, and are rapid. The results presented here demonstrate the versatility of DNA-based platforms for the detection of bispecific antibodies and could represent a versatile alternative to other more reagent-intensive and time-consuming analytical approaches.

Antibodies are among the most relevant biomolecular targets for diagnostic and clinical applications. In this Perspective, we provide a critical overview of recent research efforts focused on the development and characterization of devices, switches, and reactions based on the use of synthetic antigen-conjugated DNA strands designed to be responsive to specific antibodies. These systems can find applications in sensing, drug-delivery, and antibody-antigen binding characterization. The examples described here demonstrate how the programmability and chemical versatility of synthetic nucleic acids can be used to create innovative analytical tools and target-responsive systems with promising potentials.

We report here the development of an electrochemical cell-free biosensor for antibody detection directly in complex sample matrices with high sensitivity and specificity that is particularly suitable for point-of-care applications. The approach is based on the use of programmable antigen-conjugated gene circuits that, upon recognition of a specific target antibody, trigger the cell-free transcription of an RNA sequence that can be consequently detected using a redox-modified probe strand immobilized to a disposable electrode. The platform couples the features of high sensitivity and specificity of cell-free systems and the strength of cost-effectiveness and possible miniaturization provided by the electrochemical detection. We demonstrate the sensitive, specific, selective, and multiplexed detection of three different antibodies, including the clinically-relevant Anti-HA antibody., (© 2022 Wiley-VCH GmbH.)

We report here the development of a cell-free in vitro transcription system for the detection of specific target antibodies. The approach is based on the use of programmable antigen-conjugated DNA-based conformational switches that, upon binding to a target antibody, can trigger the cell-free transcription of a light-up fluorescence-activating RNA aptamer. The system couples the unique programmability and responsiveness of DNA-based systems with the specificity and sensitivity offered by in vitro genetic circuitries and commercially available transcription kits. We demonstrate that cell-free transcriptional switches can efficiently measure antibody levels directly in blood serum. Thanks to the programmable nature of the sensing platform, the method can be adapted to different antibodies: we demonstrate here the sensitive, rapid, and cost-effective detection of three different antibodies and the possible use of this approach for the simultaneous detection of two antibodies in the same solution.

Current health emergencies have highlighted the need to have rapid, sensitive, and convenient platforms for the detection of specific antibodies. In response, we report here the design of an electrochemical DNA circuit that responds quantitatively to multiple specific antibodies. The approach employs synthetic antigen-conjugated nucleic acid strands that are rationally designed to induce a strand displacement reaction and release a redox reporter-modified strand upon the recognition of a specific target antibody. The approach is sensitive (low nanomolar detection limit), specific (no signal is observed in the presence of non-targeted antibodies), and selective (the platform can be employed in complex media, including 90% serum). The programmable nature of the strand displacement circuit makes it also versatile, and we demonstrate here the detection of five different antibodies, including three of which are clinically relevant. Using different redox reporters, we also show that the antibody-responsive circuit can be multiplexed and responds to different antibodies in the same solution without crosstalk.

Lay Abstract: Although young children may participate in education and intervention programs that take place in classrooms or groups, there is little information about how toddlers with special needs, and specifically toddlers with autism, are engaging with their peers. This study takes place in a public center-based early intervention program for toddlers with autism. Classrooms of toddlers were randomly assigned to an individual social communication intervention or the same intervention adapted to include a peer. Children in both groups made gains in social communication and play skills. Children who had the peer intervention were more engaged with peers when an adult was present, but not when the children were unsupported. This article adds information about early skills that may be important for children to master so that they have more success when trying to interact with their peers. These skills include understanding language (referred to as "receptive language" at 12 months or more) and play skills including building and stacking (referred to as "combination play"-for example, building with blocks or completing a puzzle) and extending familiar actions to themselves, others, and figures (referred to as "presymbolic play"-for example, putting a bottle to the doll or to themselves). Understanding which skills to target can help practitioners focus their instruction to build children's skills toward connecting with peers through play.

Intervention research is increasingly conducted in community settings, however it is not clear how well practices are sustained locally or how children progress once external research support is removed. Two school-year cohorts of toddlers with autism (year 1: n = 55, year 2: n = 63) received Joint Attention, Symbolic Play, Engagement, and Regulation (JASPER) intervention from teaching assistants (TAs) with external support in year 1 and local, internal support in year 2. TAs sustained intervention strategies with more modest maintenance of high-level skills. Children in both years 1 and 2 made similar gains in initiations of joint attention during independent assessment. Year 1 children made significantly greater play gains. JASPER sustained into year 2, however advancing play may require additional supports.

Background: Interventions found to be effective in research settings are often not as effective when implemented in community settings. Considering children with autism, studies have rarely examined the efficacy of laboratory-tested interventions on child outcomes in community settings using randomized controlled designs., Methods: One hundred and thirteen children with autism enrolled in public early intervention classrooms in low resource neighborhoods were randomized to Joint Attention, Symbolic Play, Engagement, and Regulation (JASPER) intervention or treatment as usual waitlist for 10 weeks with 1-month follow-up., Results: Teaching assistants delivered JASPER at adequate fidelity. Children randomized to JASPER demonstrated significant gains over treatment as usual in core developmental outcomes of joint engagement, joint attention, and play skills that were maintained at follow-up., Conclusions: Supervised teaching assistants delivered JASPER intervention with a range of toddlers with autism leading to significant gains in developmental outcomes., (© 2016 Association for Child and Adolescent Mental Health.)