Toggle light / dark theme

I am pleased to announce that my lead-author review paper has been published in ACS Nano! If you are interested in learning about the convergence of synthetic biology and adenoviral gene therapy, I encourage you to check out my paper.

If you cannot access the full text, I have also posted a local copy at the following link: https://logancollinsblog.files.wordpress.com/2021/08/synthet…s-2021.pdf.

#ACS #ACSNano #SyntheticBiology #GeneTherapy #Biology #Biotech #Science #Biotechnology #Nanotechnology #Adenovirus #Engineering #Virology


Synthetic biology centers on the design and modular assembly of biological parts so as to construct artificial biological systems. Over the past decade, synthetic biology has blossomed into a highly productive field, yielding advances in diverse areas such as neuroscience, cell-based therapies, and chemical manufacturing. Similarly, the field of gene therapy has made enormous strides both in proof-of-concept studies and in the clinical setting. One viral vector of increasing interest for gene therapy is the adenovirus (Ad). A major part of the Ad’s increasing momentum comes from synthetic biology approaches to Ad engineering. Convergence of gene therapy and synthetic biology has enhanced Ad vectors by mitigating Ad toxicity in vivo, providing precise Ad tropisms, and incorporating genetic circuits to make smart therapies which adapt to environmental stimuli. Synthetic biology engineering of Ad vectors may lead to superior gene delivery and editing platforms which could find applications in a wide range of therapeutic contexts.

Many drugs show promising results in laboratory research but eventually fail clinical trials. We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stroma interactions, which are essential for proper representation of cancer complexed biology. Therefore, we recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells. We observed similar growth curves, drug response, and genetic signature of glioblastoma cells grown in our 3D-bioink platform and in orthotopic cancer mouse models as opposed to 2D culture on rigid plastic plates. Our 3D-bioprinted model could be the basis for potentially replacing cell cultures and animal models as a powerful platform for rapid, reproducible, and robust target discovery; personalized therapy screening; and drug development.

Cancer is the second leading cause of death globally. It is estimated that around 30 to 40% of patients with cancer are being treated with ineffective drugs ; therefore, preclinical drug screening platforms attempt to overcome this challenge. Several approaches, such as whole-exome or RNA sequencing (RNA-seq), aim to identify druggable, known mutations or overexpressed genes that may be exploited as a therapeutic target for personalized therapy. More advanced approaches offer to assess the efficacy of a drug or combinations of drugs in patient-derived tumor xenograft models or in vitro three-dimensional (3D) organoids. Unfortunately, most of the existing methods face unmet challenges, which limit their efficacy. For instance, cells can become quiescent or acquire somatic mutations while growing many generations on plastic under the influence of static mechanical forces and in the absence of functional vasculature.

Investigators who previously developed a recipe for turning skin cells into primitive muscle-like cells that can be maintained indefinitely in the lab without losing the potential to become mature muscle have now uncovered how this recipe works and what molecular changes it triggers within cells. The research, which was led by scientists at Massachusetts General Hospital (MGH) and is published in Genes & Development, could allow clinicians to generate patient-matched muscle cells to help treat muscle injuries, aging-related muscle degeneration, or conditions such as muscular dystrophy.

It’s known that expression of a regulatory gene called MyoD is sufficient to directly convert into mature ; however, mature muscle do not divide and self-renew, and therefore they cannot be propagated for clinical purposes. “To address this shortcoming, we developed a system several years ago to convert skin cells into self-renewing muscle stem-like cells we coined induced myogenic progenitor cells, or iMPCs. Our system uses MyoD in combination with three chemicals we previously identified as facilitators of cell plasticity in other contexts,” explains senior author Konrad Hochedlinger, Ph.D., a principal investigator at the Center for Regenerative Medicine at MGH and a professor of medicine at Harvard Medical School.

In this latest study, Hochedlinger and his colleagues uncovered the details behind how this combination converts skin cells into iMPCs. They found that while MyoD expression alone causes skin cells to take on the identity of mature muscle cells, adding the three chemicals causes the skin cells to instead acquire a more primitive stem cell–like state. Importantly, iMPCs are molecularly highly similar to muscle tissue stem cells, and muscle cells derived from iMPCs are more stable and mature than muscle cells produced with MyoD expression alone.

What is causing chronic inflammation?


Summary: A new study adds to the growing body of research linking inflammation to depression. Researchers found the molecule histamine directly inhibits the release of serotonin in the brain by attaching to inhibitory receptors on serotonin neurons in mice.

Source: Imperial College London

The findings, from researchers at Imperial College London and University of South Carolina, add to mounting evidence that inflammation, and the accompanying release of the molecule histamine, affects a key molecule responsible for mood in the brain – serotonin.

If replicated in humans, the findings – which identify histamine as a ‘new molecule of interest’ in depression – could open new avenues for treating depression, which is the most common mental health problem worldwide.

In the study, researchers in the laboratory of Anna Penn, MD, Ph.D., now at Columbia University Vagelos College of Physicians and Surgeons and previously at Children’s National Hospital in Washington, D.C., found that reducing amounts of a single hormone, called allopregnanolone (ALLO), in the placenta caused brain and behavior changes in male offspring that resemble changes seen in some people with autism spectrum disorder. The study also found that both brain structure and behavioral changes in the mice could be prevented with a single injection of ALLO in late pregnancy.


Preterm birth has been shown to increase the risk of autism spectrum disorders and other developmental problems, particularly in males. The more premature a baby is, the greater the risk of either motor or cognitive deficits. What does the preterm baby lose that is so critical to long-term outcomes?

A new study, in mice, suggests that one factor may be the loss of a placental hormone that the developing would normally see in the second half of pregnancy.

The study is the first to provide direct evidence that loss of a placental hormone alters long-term brain development.