Viral vector systems have been developed with enhanced safety features as described above. Resulting particles are replication-incompetent and deletion in the U3 portion of the 3’ LTR eliminates the promoter-enhancer region, further negating the possibility of viral replication. The system has also removed virulence genes which are not necessary for viral packaging. In combination, these features have improved biosafety and handling. It is recommended to use a third generation transfer vector for its enhanced biosafety features. While there is no documented occurrence of third generation transfer vectors producing replication competent virus, it is important to monitor for replication competency when performing routine lentiviral packaging. NIH guidelines recommend replication-incompetent lentiviral particles be handled as Risk Group-Level 2 (RGL2). Additional precautions may be required based upon local, state, or country regulations.