Recombinant DNA Advisory Committee - 03/1-2/93 
however, the env remains which could allow for homologous recombination. 
Dr. Haselkorn asked if the RAC is being asked to consider a vector that has not been 
thoroughly tested. Dr. Miller responded that the proposed vector has been tested 
extensively; however, the committee should consider the theoretical probability of such 
an event. Dr. Haselkorn said that it is imperative that the investigators address the issue 
of helper virus in their responses to the committee. 
Dr. Walters noted that two RAC members, Drs. Chase and Leventhal, have recused 
themselves from reviewing and voting on this protocol because they are employees of 
Johns Hopkins University, and do not want to present the appearance of conflict of 
interest. Dr. Walters called on Dr. Simons to respond the questions and comments of 
the RAC members. 
Presentation-Dr. Simons 
Dr. Simons introduced his co-investigators: Drs. Richard Mulligan, Glen Dranoff, Larry 
Cohen, Fray Marshall, William Nelson, Drew Pardoll, Steven Pianadori, Elizabeth Jaffe, 
Karen Hauda, Jim Zabora, and Beth Gregory. Dr. Simons stated that Dr. Mulligan 
would address the RAC members' questions and comments about the MFG and MFGS 
vectors. 
Dr. Mulligan said that, in general, he agreed with Dr. Miller's comment that there is no 
packaging cell line that is absolutely safe. The vector has an open reading frame that 
expresses the pl5 protein. One of the positive features of this vector is that it possesses 
extra packaging sequences. When the desired sequences are inserted into the vector, the 
protein which is expressed is very similar to the normal protein and is very efficiently 
expressed. 
In terms of safety, this vector has been tested extensively in the packaging cell line, Y- 
crip. Dr. Mulligan stated that there have not been any concerns about the existence of 
open reading frames in this vector. He said that 30 separate constructs have been made 
and that no helper virus production was detected in any case. The assays for the 
detection of helper virus have been performed in-house as well as by reliable outside 
laboratories. 
Dr. Mulligan stated that they attempted to introduce simple changes that would increase 
the safety potential of the MFG vector; this safety modified vector is MFGS. A stop 
codon has been introduced in MFGS in order to inhibit the open reading frame from 
initiating pl5 protein production. The key factors that were considered in evaluating this 
modified vector as compared to the parent vector were: (1) the efficiency of gene 
transfer, (2) level of gene expression, and (3) the immune effects observed in relation to 
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