A Cell-Permeant Nanobody-Based Degrader That Induces Fetal Hemoglobin.

Proximity-based strategies to degrade proteins have enormous therapeutic potential in medicine, but the technologies are limited to proteins for which small molecule ligands exist. The identification of such ligands for therapeutically relevant but "undruggable" proteins remains challenging. Herein, we employed yeast surface display of synthetic nanobodies to identify a protein ligand selective for BCL11A, a critical repressor of fetal globin gene transcription. Fusion of the nanobody to a cell-permeant miniature protein and an E3 adaptor creates a degrader that depletes cellular BCL11A in differentiated primary erythroid precursor cells, thereby inducing the expression of fetal hemoglobin, a modifier of clinical severity of sickle cell disease and ß-thalassemia. Our strategy provides a means of fetal hemoglobin induction through reversible, temporal modulation of BCL11A. Additionally, it establishes a new paradigm for the targeted degradation of previously intractable proteins.

Internet use by physicians and its impact on medical practice-an exploratory study.

Internet use by physicians has played a vital role in medical practices for many years. A number of related studies have emerged to examine the impact of Internet use on medical practice. However, there is yet to be a comprehensive study on the impact of Internet use by physicians on their medical practice. This study examines a preliminary step to explore the major implications of physicians' Internet use on the traditional areas, such as health education and learning, physician-patient relationship, and medical marketing. Barriers to Internet use are also investigated. Implication of use of the Internet in the medical practice and limitations of this study are discussed as well.