Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington's Disease.

Huntington's disease is a genetic disorder characterized by progressive neuronal cell damage in some areas of the brain; symptoms are commonly associated with chorea, rigidity and dystonia. The symptoms in Huntington's Disease are caused by a pathological increase in the number of Cytokine-Adenine-Guanine (CAG) repeats on the first exon of the Huntingtin gene, which causes a protein to have an excessive number of glutamine residues; this alteration leads to a change in the protein's conformation and function. Therefore, the purpose of this work was to design, synthesize and evaluate an antisense oligonucleotide (ASO; 95 nucleotides) HTT 90-5 directed to the Huntingtin CAG repeats in primary leukocyte culture cells from a patient with Huntington's Disease; approximately 500,000 leukocytes per well extracted from venous blood were used, to which 100 pMol of ASO were administered, and the expression of Huntingtin was subsequently evaluated at 72 h by RT-PCR.

siRNA Targeting ECE-1 Partially Reverses Pulmonary Arterial Hypertensionassociated Damage in a Monocrotaline Model.

Aims: The aim of this study was to develop a possible treatment for pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a rare disease characterised by a pulmonary arterial pressure greater than 20 mmHg. One of the factors that contribute to PAH is an increase in the production of endothelin-1, a polypeptide that increases vascular resistance in the pulmonary arteries, leading to increased pulmonary arterial pressure and right ventricular hypertrophy.

siRNA knockdown of angiopoietin 2 significantly reduces neovascularization in diabetic rats.

Diabetes is a disease that leads to proliferative diabetic retinopathy (PDR), which is associated with an increase of new vessels formation due to an overexpression of angiogenic factors, such as angiopoietin 2 (ANGPT2). The aim of this work was to design a siRNA targeting ANGPT2 to decrease the retinal neovascularization associated with PDR. Adult male Wistar rats weighing 325-375 g were used.