Two items relevant to long COVID

One of the tricky issues in studying in long COVID is: how widely do researchers cast their net? Initial reports acknowledged that people who were hospitalized and in intensive care may take a while to get back on their feet. But the number of people who had SARS-CoV-2 infections and were NOT hospitalized, yet experienced lingering symptoms, may be greater. A recent report from the United Kingdom, published in PLOS Medicine, studied more than Read more

All your environmental chemicals belong in the exposome

Emory team wanted to develop a standard low-volume approach that would avoid multiple processing steps, which can lead to loss of material, variable recovery, and the potential for Read more

Signature of success for an HIV vaccine?

Efforts to produce a vaccine against HIV/AIDS have been sustained for more than a decade by a single, modest success: the RV144 clinical trial in Thailand, whose results were reported in 2009. Now Emory, Harvard and Case Western Reserve scientists have identified a gene activity signature that may explain why the vaccine regimen in the RV144 study was protective in some individuals, while other HIV vaccine studies were not successful. The researchers think that this signature, Read more

TJ Cradick

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