Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

gene editing

Viral vectors ready for delivery

The phrase “viral vector” sounds ominous, like something from a movie about spies and internet intrigue. It refers to a practical delivery system for the gene of your choice. If you are a biomedical researcher and you want to tweak genes in a particular part of the body in an experimental animal, viral vectors are the way to go.

Viral vector-transduced retinal ganglion cell; dendrites and axons labeled with GFP. Courtesy Felix Struebling via Xinping Huang

Emory’s Viral Vector Core was started when eminent neuroscientist Kerry Ressler was at Emory and is now overseen by geneticist Peng Jin. Technical director Xinping Huang and her colleagues can produce high-titer viral vectors, lentivirus and AAV. Discuss with her the best choice. It may depend on the size of the genetic payload you want to deliver and whether you want the gene to integrate into the genome of the target cell.

As gene therapy and CRISPR/Cas9-style gene editing research progresses, we can anticipate demand for services such as those provided by the Viral Vector Core. [Clinical applications are close, but will not be dealt with in the same place!] Read more

Posted on by Quinn Eastman in Neuro Leave a comment

CRISPR gene editing can miss its mark

Yanni Lin, TJ Cradick, Gang Bao and colleagues from Georgia Tech and Emory reported recently in Nucleic Acids Research on how the CRISPR/Cas9 gene editing system can sometimes miss its mark.

CRISPR/Cas9 has received abundant coverage from science-focused media outlets. Basically, it is a convenient system for cutting DNA in cells in a precise way. This paper shows that the CRISPR/Cas9 system can sometimes cut DNA in places that don’t exactly match the designed target.

Here we show that CRISPR/Cas9 systems can have off-target cleavage when DNA sequences have an extra base or a missing base at various locations compared with the corresponding RNA guide strand…Our results suggest the need to perform comprehensive off-target analysis by considering cleavage due to DNA and sgRNA bulges in addition to base mismatches.

CRISPR/Cas9 could be used to develop therapies for humans for genetic blood diseases such as sickle cell or thalassemia, and this paper does not change that potential. But the authors are cautioning fellow scientists that they need to design their tools carefully and perform quality control. Other investigators have made similar findings.

Posted on by Quinn Eastman in Uncategorized Leave a comment

Addendum on CRISPR

An excellent example of the use of CRISPR gene editing technology came up at the Emory-Children’s Pediatric Research Center’s Innovation Conference this week.

Marcela Preininger, who is working with cardiomyocyte stem cell specialist Chunhui Xu, described her work (poster abstract 108) on cells derived from a 12 year old patient with an inherited cardiac arrhythmia syndrome: catecholaminergic polymorphic ventricular tachycardia or CPVT. Her team has obtained skin fibroblasts from the patient, and converted those cells into induced pluripotent stem cells, which can then be differentiated into cardiac muscle cells or cardiomyocytes.

Working with TJ Cradick, director of the Protein Engineering Facility at Georgia Tech, Preininger is testing out CRISPR gene editing as a means of correcting the defect in this patient’s cells, outside the body. Cradick says that while easy and efficient, RNA-directed CRISPR can be lower in specificity compared to the protein-directed TALEN technology.

From Preininger’s abstract:

Once the mutation has been corrected at the stem cell level, we will investigate whether the repaired (mutation-free) iPS cells can be differentiated into functional cardiomyocytes with normal Ca2+ handling properties, while closely monitoring the cells for mutagenic events. Pharmacological restoration of the normal myocardial phenotype will also be optimized and explored in our model.

Posted on by Quinn Eastman in Heart Leave a comment