Editing the Human Genome with CRISPR/Cas: A Review of its Molecular Basis, Current Clinical Applications, and Bioethical Implications.

Abstract: CRISPR/Cas genes evolved in prokaryotic organisms as a mechanism of defense designed to identify and destroy genetic material from threatening viruses. A breakthrough discovery is that CRISPR/Cas system can be used in eukaryotic cells to edit almost any desired gene. This comprehensive review addresses the most relevant work in the CRISPR/Cas field, including its history, molecular biology, gene editing capability, ongoing clinical trials, and bioethics. Although the science involved is complex, we intended to describe it in a concise manner that could be of interest to diverse readers, including anyone dedicated to the treatment of patients who could potentially benefit from gene editing, molecular biologists, and bioethicists. CRISPR/Cas has the potential to correct inherited diseases caused by single point mutations, to knock-in the promoter of a gene whose expression is highly desirable or knockout the gene coding for a deleterious protein. CRISPR/Cas technique can also be used to edit ex vivo immune cells and reinsert them in patients, improving their efficiency in attacking malignant cells, limiting the infectious potential of viruses or modulating xenotransplant rejection. Very important bioethical considerations on this topic include the need to internationally regulate its use by ad hoc expert committees and to limit its use until safety and bioethical issues are satisfactorily resolved.

Editing the Human Genome with CRISPR/Cas: A Review of its Molecular Basis, Current Clinical Applications, and Bioethical Implications

ABSTRACT CRISPR/Cas genes evolved in prokaryotic organisms as a mechanism of defense designed to identify and destroy genetic material from threatening viruses. A breakthrough discovery is that CRISPR/Cas system can be used in eukaryotic cells to edit almost any desired gene. This comprehensive review addresses the most relevant work in the CRISPR/Cas field, including its history, molecular biology, gene editing capability, ongoing clinical trials, and bioethics. Although the science involved is complex, we intended to describe it in a concise manner that could be of interest to diverse readers, including anyone dedicated to the treatment of patients who could potentially benefit from gene editing, molecular biologists, and bioethicists. CRISPR/Cas has the potential to correct inherited diseases caused by single point mutations, to knock-in the promoter of a gene whose expression is highly desirable or knockout the gene coding for a deleterious protein. CRISPR/Cas technique can also be used to edit ex vivo immune cells and reinsert them in patients, improving their efficiency in attacking malignant cells, limiting the infectious potential of viruses or modulating xenotransplant rejection. Very important bioethical considerations on this topic include the need to internationally regulate its use by ad hoc expert committees and to limit its use until safety and bioethical issues are satisfactorily resolved.

Acute Mitral Regurgitation Due to Chordae Tendineae Rupture: A Rare Presentation of Cardiac Amyloidosis.

BACKGROUND In cardiac amyloidosis (CA), misfolded proteins deposit in the extracellular space of cardiac tissue. These deposits classically cause restrictive cardiomyopathy with diastolic dysfunction. Although there are at least 30 proteins known to cause amyloid aggregates, 2 main types make up most diagnosed cases: light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). Since CA is considered a rare condition, it is often underdiagnosed or recognized in the advanced stages. Once amyloid deposits involve the heart tissue, they are associated with a worse outcome and higher mortality rates, especially in patients presenting symptoms of heart failure. CASE REPORT We report a case of a 22-year-old man presenting with acute severe mitral regurgitation, secondary to posterior mitral leaflet chordae tendineae rupture (CTR). Surgical mitral valve replacement with a mechanical prosthesis was performed, and cardiac tissue biopsy samples were obtained. After surgery, the patient improved significantly but suddenly presented with hemodynamic deterioration, until he died due to severe hemodynamic compromise and multiorgan failure. Although the etiology of the CTR was not established before surgical intervention, the histopathological analysis suggested CA. CONCLUSIONS CA diagnosis can be complex, especially in a 22-year-old-man with atypical clinical and imaging manifestations. In this patient, other differential diagnoses were considered, since CA presenting in a young patient is a rare phenomenon and acute mitral regurgitation secondary to CTR presents more frequently in other heart conditions. Furthermore, rapid postoperative deterioration resulted in the patient's death before biopsy samples were available because suspicion of amyloidosis had not been raised until that point.