Skin penetrating polypeptide and pharmaceutical compositions and methods of use thereof are provided. Typically, the peptides are between 3 and 100 amino acids, more preferably about 5, 6, 7, 8, 9, or 10 amino acids, cyclic, binds to a skin protein such as a keratin with a Kd of between about 10-3 M and about 10-8 M. Preferably the peptides increase absorption or penetration of an active agent into the skin. In silico methods of screening for skin protein binding polypeptides are also provided.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Disclosed herein are novel analogs of cyclosporin, pharmaceutical compositions containing them, and methods for their use in the treatment of dry eye and other conditions.

The invention is directed to a system comprising a lentivirus vector particle which encodes at least one guide RNA sequence that is complementary to a first DNA sequence in a host cell genome, a Cas9 protein, and optionally a donor nucleic acid molecule comprising a second DNA sequence. The invention also is directed to a method of altering a DNA sequence in a host cell using such a system, where the host cell can be in a human and the altered DNA can be of the human -globin gene. The invention also is directed to a fusion protein comprising a Cas9 protein and a cyclophilin A (CypA) protein. The invention also is directed to sequences of vectors that can be used in the system and method.

Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Provided are novel types of hybrid cyclic libraries that contain a known protein binding domain of a natural product. Also provided are synthetic methods to make such libraries and methods for the deconvolution of hits using partially split-pooled library compounds. Such methods are applicable for use with the entire human proteome to screen such libraries that bind and for the identification of hits.

Disclosed herein are autoclavable formulations of cyclosporin A Form 2, methods of making such formulations, and methods of treating diseases of the eye with such formulations.

Use of cyclosporin H (CsH) or a derivative thereof for increasing the efficiency of transduction of an isolated population of cells by a viral vector and/or increasing the efficiency of gene editing of an isolated population of cells when transduced by a viral vector.

Compounds defined by Formula 4 are used as cyclophilin inhibitors for the prevention or treatment of diseases or disorders, in particular diseases or conditions associated with cellular injury or cell death, such as organ injury or organ failure, which can be caused by a number of different reasons, such as ischemia or ischemia reperfusion injury, toxins, infection or mechanical trauma.

Disclosed herein are methods of making cyclosporin A Form 2.