Characterization of the TLR9-Activating Potential of LNA-Modified Antisense Oligonucleotides.

Early characterization of the immunostimulatory potential of therapeutic antisense oligonucleotides (ASOs) is crucial. At present, little is known about the toll-like receptor 9 (TLR9)-mediated immunostimulatory potential of third-generation locked nucleic acid (LNA)-modified ASOs. In this study, we have systematically investigated the TLR9-activating potential of LNA-modified oligonucleotides using different mouse and human cell culture systems.

Human angiotensin-converting enzyme 2-specific antisense oligonucleotides reduce infection with SARS-CoV-2 variants.

Background: The Spike protein mutation severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to decreased protective effect of various vaccines and mAbs, suggesting that blocking SARS-CoV-2 infection by targeting host factors would make the therapy more resilient against virus mutations. Angiotensin-converting enzyme 2 (ACE2) is the host receptor of SARS-CoV-2 and its variants, as well as many other coronaviruses. Downregulation of ACE2 expression in the respiratory tract may prevent viral infection.

Preventing ATP Degradation by ASO-Mediated Knockdown of CD39 and CD73 Results in A2aR-Independent Rescue of T Cell Proliferation.

The adenosine axis contributes to the suppression of antitumor immune responses. The ectonucleotidase CD39 degrades extracellular adenosine triphosphate (ATP) to adenosine monophosphate (AMP), which is degraded to adenosine by CD73. Adenosine binds to, e.

A highly efficient modality to block the degradation of tryptophan for cancer immunotherapy: locked nucleic acid-modified antisense oligonucleotides to inhibit human indoleamine 2,3-dioxygenase 1/tryptophan 2,3-dioxygenase expression.

Tumors can utilize a diverse repertoire of immunosuppressive mechanisms to evade attack by the immune system. Despite promising success with blockade of immune checkpoints like PD-1 the majority of patients does not respond to current immunotherapies. The degradation of tryptophan into immunosuppressive kynurenine is an important immunosuppressive pathway.

Antisense oligonucleotide targeting CD39 improves anti-tumor T cell immunity.

Background: Cancer cells are known to develop mechanisms to circumvent effective anti-tumor immunity. The two ectonucleotidases CD39 and CD73 are promising drug targets, as they act in concert to convert extracellular immune-stimulating ATP to adenosine. CD39 is expressed by different immune cell populations as well as cancer cells of different tumor types and supports the tumor in escaping immune recognition and destruction.

Assessing Foot Loads in Continuous Passive Motion (CPM) and Active Knee Joint Motion Devices.

Background: Continuous passive motion (CPM) and active knee joint motion devices are commonly applied after various surgical procedures. Despite the growing use of active motion devices, there is a paucity of data comparing plantar loads between the different mobilization techniques. The aim of this study was to investigate foot loads during knee joint mobilization in continuous passive and active knee joint motion devices and to compare this data to the physiological load of full weight-bearing.