Science Editor

Editor s note: Science Scan is a roundup of recently published biotechnology-relevant research.

The discovery of a new gene that encodes an adhesion protein critical for hair growth might someday throw light on alopesia (baldness), and hair-removal treatments for hirsutism (excess hairiness).

A report of this potential twin hair loss and gain appears in the journal Cell, dated April 17, 2003. Its title: Desmoglein 4 is essential for hair follicle keratinocyte differentiation and epidermal adhesion: Evidence from inherited hypotrichosis [scanty hair] and acquired pemphigus vulgaris [autoimmune blistered-skin disease]. Its authors are geneticists and dermatologists at Columbia University in New York.

The newly-revealed protein, desmoglein 4 (DSG4), holds cells together as they change into one of many different types of hair-follicle cells. DSG4 ensures that each cell is in the right place at the right time as it marches alongside the others when the hair shaft is formed. The senior author of the paper, Angela Christiano, compared the protein to Velcro. If they don t stick together properly, she pointed out in a press statement, they become disconnected from their neighbors, and can t receive instructions properly.

Without DSG4, she added, the cells separate from each other and become disorganized. Rather than the six ordered layers of a normal hair fiber, you get a cluster of confused cells in the hair follicle. As a result, people and mice lacking the desmoglein gene have thin, sparse hair that is fragile, and breaks easily.

DSG4 is the third gene found in Christiano s lab to have a role in human hair growth. It s the first of the three that codes for a structural protein, which becomes part of the hair follicle s bricks and mortar. All three genes, Christiano predicted, could have roles in gene therapy designed for hair removal, both temporary and permanent. Remarkably, she observed, hair growth is a medical problem for which people want treatment on both sides of the spectrum too much and too little. It s of interest to both men and women.

One such treatment strategy, she noted, will be to use products containing ribozymes or antisense. By binding to the RNAs in this way, the antisense molecule inactivates it, and thus the protein it encodes will not be expressed. Even inactivating one of the two regulatory genes stopped hair growth in mice permanently.

According to the university s technology transfer unit, a start-up company, Skinetics Bioscience LLC, is being formed to develop hair-growth and hair-removal products. Christiano envisages starting clinical trials for hair removal by mid-winter.

Summing up, the Cell paper noted, The essential role of desmoglein 4 in skin was established by identifying mutations in families with inherited hypotrichosis [scant body hair]. We also show that DSG4 is an autoantigen in pemphigus vulgaris. Finally, we provide evidence that desmoglein 4 is a key mediator of keratinocyte cell adhesion in the hair follicle, where it coordinates the transition from proliferation to differentiation.

Nanometer-Scale Particles, Escorted Through Cell Membranes By Micelles, Enhance Drug Delivery

To explore new possibilities for targeting drug delivery at the subcellular level, researchers tracked sub-tiny molecular globs called micelles as they traveled into living cells. Spherical micelles, they found, could form nanocontainers to transport insoluble drugs through cell membranes. Their paper in Science, dated April 25, 2003, is titled Micellar nanocontainers distribute to defined cytoplasmic organelles. Its authors are at McGill University in Montreal.

Using novel fluorescent labeling methods, they could see that micelles, once inside a cell, do not enter the nucleus. Instead, they penetrate specific organelles, such as mitochondria and Golgi apparatus, which could be important targets for drug delivery. In addition, they found that micelles deliver their contents to the cell very efficiently, which could minimize the amount of toxic medications needed.

A commentary headed Enhancing drug function makes the point that micelles are particularly attractive for drug delivery, because they do not require the chemical identity of the drug to be changed. The drug can be loaded into the core of the micelle. Administration of micelle-incorporated drugs achieves several positive effects at once. On the level of the whole body, the drug is solubilized, avoiding use of the hydrophobic carriers usually used to deliver the drugs. On the level of the tumor and even its metastases, the leakiness of the tumor blood vessels allows the colloidal particles to preferentially accumulate in the tumor.

Eyeing Adeno-Associated Virus As Potential Gene Therapy Vector Turns Up AAV In Primate Species

Adeno-associated viruses (AAVs) are endemic in the human population, in which they cause no known harm. In order to replicate, AAV depends on adeno-virus (AV), which is widely used as a vector in gene therapy experiments. But AV has several salient drawbacks, so gene therapists are casting an experimental eye on replacing it with AAV.

To better understand its biology, scientists at the Wistar Institute in Philadelphia examined a number of nonhuman primate species for the presence of previously uncharacterized AAV. They found widely disseminated AAV genomes throughout multiple tissues of Rhesus macaques and other monkey varieties. They detected surprising diversity of sequence, primarily localized to hypervariable regions of the capsid protein.

Their paper, in the Proceedings of the National Academy of Sciences (PNAS), was released online April 22, 2003. Its title: Adeno-associated viruses undergo substantial evolution in primates during natural infections. The report attributes this sequence diversity in part to homologous recombination of co-infecting parental viruses that modify the serologic reactivity and tropism of the virus. This is an example of rapid molecular evolution of a DNA virus in a way that was thought formerly to be restricted to RNA viruses. The PNAS article concludes: The implications of this work for application of AAV in gene therapy is unclear, although the wide distribution of endogenous latent virus together with a propensity to rearrange might be a topic of further studies in the context of in vivo gene transfer to animals and humans.