The following recombinant or synthetic nucleic acid molecules are exempt from the NIH Guidelines and registration with the Institutional Biosafety Committee is not required; however, other federal and state standards of biosafety may still apply to such research (for example, the Centers for Disease Control and Prevention (CDC)/NIH publication Biosafety in Microbiological and Biomedical Laboratories).

1. Those synthetic nucleic acids that: (1) can neither replicate nor generate nucleic acids that can replicate in any living cell (e.g., oligonucleotides or other synthetic nucleic acids that do not contain an origin of replication or contain elements known to interact with either DNA or RNA polymerase), and (2) are not designed to integrate into DNA, and (3) do not produce a toxin that is lethal for vertebrates at an LD50 of less than 100 nanograms per kilogram body weight. If a synthetic nucleic acid is deliberately transferred into one or more human research participants and meets the criteria of Section III-C, it is not exempt under this Section.

2. Those that are not in organisms, cells, or viruses and that have not been modified or manipulated (e.g., encapsulated into synthetic or natural vehicles) to render them capable of penetrating cellular membranes.

3. Those that consist solely of the exact recombinant or synthetic nucleic acid sequence from a single source that exists contemporaneously in nature.

8. Those that do not present a significant risk to health or the environment (see Section IV-C-1-b-(1)-(c), Major Actions), as determined by the NIH Director following appropriate notice and opportunity for public comment. See Appendix C, Exemptions under Section III-F-8 for other classes of experiments which are exempt from the NIH Guidelines.

Appendix C-II. Escherichia coli K-12 Host-Vector Systems.

Experiments which use Escherichia coli K-12 host-vector systems, with the exception of those experiments listed in Appendix C-II-A, are exempt from the NIH Guidelines provided that: (i) the Escherichia coli host does not contain conjugation proficient plasmids or generalized transducing phages; or (ii) lambda or lambdoid or Ff bacteriophages or non-conjugative plasmids (see Appendix C-IX-B, Footnotes and References of Appendix C) shall be used as vectors. However, experiments involving the insertion into Escherichia coli K-12 of DNA from prokaryotes that exchange genetic information (see Appendix C-IX-C, Footnotes and References of Appendix C) with Escherichia coli may be performed with any Escherichia coli K-12 vector (e.g., conjugative plasmid). When a non-conjugative vector is used, the Escherichia coli K-12 host may contain conjugation-proficient plasmids either autonomous or integrated, or generalized transducing phages. For these exempt laboratory experiments, Biosafety Level (BL) 1 physical containment conditions are recommended. For large-scale fermentation experiments, the appropriate physical containment conditions need be no greater than those for the host organism unmodified by recombinant or synthetic nucleic acid molecule techniques; the Institutional Biosafety Committee can specify higher containment if deemed necessary.