Penetrating the Barrier: Delivery of Active Proteins into Cells

Release Date:
Alisa Zapp Machalek, NIGMS

One of the biggest problems in the pharmaceutical industry is getting drugs, especially large protein molecules, into appropriate tissues and cells. Scientists have unsuccessfully tried to force proteins into living cells using myriad techniques, including micro-injection needles, micro-guns, and chemical agents that punch holes in cells.

Now, NIGMS grantee Dr. Yao-Zhong Lin and his colleagues at Vanderbilt University have imported entire protein molecules into mammalian cells. They accomplished this by adapting the cells� own targeting equipment. Once inside, the proteins functioned normally, overcoming yet another challenge. The technique is simple and inexpensive, and not surprisingly, it has already attracted the attention of several pharmaceutical companies.

Proteins manufactured inside our cells each have a specific destination within or outside the cell. Often, this destination is specified on the protein like a mailing label on an envelope. When Dr. Lin�s group attached similar cellular mailing labels--officially called signal peptide sequence--to test proteins, they were able to import the proteins into a variety of mammalian cells.

The researchers have used this technique to import relatively large proteins. Currently, pharmaceutical companies try to keep drug molecules small so they are easily absorbed. By enabling the import of much larger proteins, Dr. Lin�s technique may not only increase the ability of existing drugs to reach their targets, but may also open up new avenues for drug and vaccine development. For example, diseases like cystic fibrosis and sickle cell anemia that result from defects in a single protein could theoretically be treated by importing normal versions of the defective proteins. The work also will provide cell biologists with another tool to study the effect of individual proteins, adding to their understanding of cellular processes and potentially revealing new drug targets.


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Reporters may call Alisa Zapp Machalek at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Cell Biology and Biophysics who can comment on this work.