Formulation development and feasibility of AAV5 as a lyophilized drug product.

The majority of adeno-associated virus (AAV) gene therapies are currently developed as frozen formulations (e.g., ≤ - 60 °C) that are challenging to maintain and distribute world-wide.

Structure of a Cyclic Peptide as an Inhibitor of Transcription: NMR and Molecular Dynamics Simulations.

Background And Objectives: A novel antitubercular cyclic peptide, Cyclo(1,6)-Ac-CLYHFC-NH, was designed to bind at the rifampicin (RIF) binding site on the RNA polymerase (RNAP) of (MTB). This peptide inhibits RNA elongation in the MTB transcription initiation assay in the nanomolar range, which can halt the MTB transcription initiation complex, similar to RIF. Therefore, determining the solution conformation of this peptide is useful in improving the peptide's binding affinity to the RNAP.

Delivery of Neuroregenerative Proteins to the Brain for Treatments of Neurodegenerative Brain Diseases.

Neurodegenerative brain diseases such as Alzheimer's disease (AD), multiple sclerosis (MS), and Parkinson's disease (PD) are difficult to treat. Unfortunately, many therapeutic agents for neurodegenerative disease only halt the progression of these diseases and do not reverse neuronal damage. There is a demand for finding solutions to reverse neuronal damage in the central nervous system (CNS) of patients with neurodegenerative brain diseases.

Mechanism of the blood-brain barrier modulation by cadherin peptides.

Aim: This study was aimed at finding the binding site on the human E-cadherin for Ala-Asp-Thr Cyclic 5 (ADTC5), ADTC7, and ADTC9 peptides as blood-brain barrier modulator (BBBM) for determining their mechanism of action in modulating the blood-brain barrier (BBB).

Methods: ADTC7 and ADTC9 were derivatives of ADTC5 where the Val6 residue in ADTC5 was replaced by Glu6 and Tyr6 residues, respectively. The binding properties of ADTC5, ADTC7, and ADTC9 to the extracellular-1 (EC1) domain of E-cadherin were evaluated using chemical shift perturbation (CSP) method in the two dimensional (2D) H-N-heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy.

Exploring How Antibody Format Drives Clearance from the Brain.

Monoclonal antibodies (mAbs) have high binding specificity and affinity, making them attractive for treating brain diseases. However, their effectiveness is limited by poor blood-brain barrier (BBB) penetration and rapid central nervous system (CNS) clearance. Our group identified blood-brain barrier modulator (BBBM) peptides that improved mAb penetration across the BBB into the brain.