A great deal of work has been done since Hannons initial work utilizing shRNAs to achieve gene knockdown in mammalian cells. An increased understanding of how the miRNA system functions in cells led to a redesign of the system. The next generation of expression constructs was designed to mimic endogenous primary miRNAs. Since the original shRNAs had mimicked pre-miRNAs, these new constructs produced molecules that entered the RNAi biochemical pathway earlier than the originals and made targeting the desired mRNA much more effective and efficient. Also, the use of lentiviral instead of retroviral vectors for delivery allowed a wider range of cell types to be targeted. Using the new strategy, Hannon and his coworkers generated a library of second generation shRNAs that targeted a substantial fraction of the genes in both the human and mouse genomes.

Researchers regularly request material from each other, but the number of requests for this collection of shRNAs would be too great for any one academic lab to fulfill. Instead, a company called OpenBio Systems was formed to handle the production and distribution of RNAi tools. Through the company website, any interested person can order RNAi products specific for nearly any human or mouse gene, or libraries covering the entire genomes of these organisms. This allows a vast number of researchers access to the latest RNAi technology which they can use to perform complex genetic screens in cell culture lines as well as animal models.

Most companies which supply biological material do not screen their orders. Some companies that provide custom DNA synthesis screen their orders to ensure that they are not providing genomes for select agents, though they are not required to do so by law. In most cases a researcher who wished to purchase and utilize RNAi tools would also have the capability, using publicly available gene sequences and standard molecular biology techniques, to produce these tools independently in their own lab.