Microfluidic Interfaces for Chronic Bidirectional Access to the Brain.

Two-photon polymerization (TPP) is an additive manufacturing technique with micron-scale resolution that is rapidly gaining ground for a range of biomedical applications. TPP is particularly attractive for the creation of microscopic three-dimensional structures in biocompatible and noncytotoxic resins. Here, TPP is used to develop microfluidic interfaces which provide chronic fluidic access to the brain of preclinical research models.

Exploring the Fate of Antibody-Encoding pDNA after Intramuscular Electroporation in Mice.

DNA-based antibody therapy seeks to administer the encoding nucleotide sequence rather than the antibody protein. To further improve the in vivo monoclonal antibody (mAb) expression, a better understanding of what happens after the administration of the encoding plasmid DNA (pDNA) is required. This study reports the quantitative evaluation and localization of the administered pDNA over time and its association with corresponding mRNA levels and systemic protein concentrations.

Intratumoral DNA-based delivery of checkpoint-inhibiting antibodies and interleukin 12 triggers T cell infiltration and anti-tumor response.

To improve the anti-tumor efficacy of immune checkpoint inhibitors, numerous combination therapies are under clinical evaluation, including with IL-12 gene therapy. The current study evaluated the simultaneous delivery of the cytokine and checkpoint-inhibiting antibodies by intratumoral DNA electroporation in mice. In the MC38 tumor model, combined administration of plasmids encoding IL-12 and an anti-PD-1 antibody induced significant anti-tumor responses, yet similar to the monotherapies.

Electroporation outperforms in vivo-jetPEI for intratumoral DNA-based reporter gene transfer.

Intratumoral delivery of drug-encoding plasmid DNA (pDNA) enables localised in vivo expression of biological drugs, offering an attractive alternative to conventional protein treatment. However, this requires physical or chemical methods to enhance the low transfection efficiency of naked pDNA. Electroporation and complexation with the polycation in vivo-jetPEI are both evaluated in the clinic for intratumoral pDNA delivery, but lack head-to-head comparison.

DNA-Based Delivery of Checkpoint Inhibitors in Muscle and Tumor Enables Long-Term Responses with Distinct Exposure.

Checkpoint-inhibiting antibodies elicit impressive clinical responses, but still face several issues. The current study evaluated whether DNA-based delivery can broaden the application of checkpoint inhibitors, specifically by pursuing cost-efficient in vivo production, facilitating combination therapies, and exploring administration routes that lower immune-related toxicity risks. We therefore optimized plasmid-encoded anti-CTLA-4 and anti-PD-1 antibodies, and studied their pharmacokinetics and pharmacodynamics when delivered alone and in combination via intramuscular or intratumoral electroporation in mice.