Publications by authors named "S L Milstein"
Background & Aims: Current therapy for chronic hepatitis B virus (cHBV) infection involves lifelong treatment. New treatments that enable HBV functional cure would represent a clinically meaningful advance. ALN-HBV and VIR-2218 are investigational RNA interference therapeutics that target all major HBV transcripts.
View Article and Find Full Text PDFA major challenge confronting the clinical application of site-directed RNA editing (SDRE) is the design of small guide RNAs (gRNAs) that can drive efficient editing. Although many gRNA designs have effectively recruited endogenous Adenosine Deaminases that Act on RNA (ADARs), most of them exceed the size of currently FDA-approved antisense oligos. We developed an unbiased in vitro selection assay to identify short gRNAs that promote superior RNA editing of a premature termination codon.
View Article and Find Full Text PDFArticle Synopsis
- - Preclinical studies indicate that off-target effects from RNA interference contribute significantly to hepatotoxicity in GalNAc-siRNA conjugates.
- - Researchers developed a new strategy called enhanced stabilization chemistry plus (ESC+) which effectively reduces off-target binding while preserving the intended on-target effects in RNA therapies.
- - This approach was successfully applied to ALN-HBV, leading to a redesigned version (ALN-HBV02) with better specificity and safety, allowing it to resume clinical development.
Article Synopsis
- Short interfering RNAs (siRNAs) have been successfully used in liver therapies, but there’s a need for new delivery methods to target other organs.
- Conjugating siRNAs with 2'-O-hexadecyl (C16) allows effective gene silencing in the central nervous system, eye, and lung, showing sustained effects for at least 3 months in animal studies.
- A study targeting amyloid precursor protein in a mouse model of Alzheimer's demonstrated that C16-siRNAs can improve both physiological and behavioral symptoms, indicating potential for broader therapeutic applications.
This research investigated the relationship consequences of disclosing sexual secrets to a romantic partner. Analyses of data from a 39-item Internet questionnaire completed by 195 undergraduate students showed that revealing sex secrets to a romantic partner was associated with either neutral or positive relationship outcomes. Disclosure of sexual secrets almost never (< 5%) resulted in relationship dissolution and over a third of the sample reported that they appreciated the honest disclosure.
View Article and Find Full Text PDF