Recombinant DNA Advisory Committee - 2/10-11/92 
have been conducted with GlNa.SvAd. Dr. Anderson stated that the informal name of 
the vector is G1SAX. All of the initial safety studies were conducted with G1SAX as with 
the previous vectors: LNL6, LN series, LASN, and GlNa.40. The modifications 
introduced into G1SAX should make it safer than the other previous vectors. 
Dr. McGarrity stated that the RAC has reviewed a series of tests for the G1 vector system. 
Differences between the G1 and LNL6 systems are: (1) a polyclonal site has been 
introduced into the G1 system; and (2) some sequences that have the potential for 
homologous recombination have been eliminated. Complete sequences of the G1 system, 
which include the neomycin resistance marker, were reviewed by Drs. Mclvor and D. 
Miller for potentially harmful sequences. If the RAC requests, Genetic Therapy, Inc., will 
submit sequences for the addition of the ADA gene. There is a description of GIN in Dr. 
Economou's proposal not including the ADA component. The description reads as 
follows: 
"This neoR vector was developed by GTI, and is virtually identical to LNL6. At 
position 1470 there are 16 additional base pairs derived from the PG1 polylinker. 
At position 2336 in GIN, 680 base pairs of 3' untranslated neoR (resistant) gene 
sequences are deleted and 36 base pairs derived from PG1N polylinker added." 
Dr. McGarrity said that the quality control and safety studies for the LNL6 system were 
completed with titers of production lots following the Food and Drug Administration 
(FDA) standards. These tests included assays for bacteria, yeast, fungi, mycoplasma, 
mouse antibody production, helper virus, S + L- xenotropic and X-C ecotropic viruses, and 
3T3 amplification. 
Dr. Mclvor asked if any safety assays have been performed specifically on the GlNa.SvAd 
vector. Dr. McGarrity replied that all the necessary assays have been performed, and the 
cell line is free of helper virus. There is no functional difference between this vector and 
LASN. Dr. Anderson stated that since the vectors are identical, the investigators wanted 
the flexibility of using either vector. However, only one of these vectors will be used to 
transduce a particular cell type. 
Ms. Buc asked if the committee could return to the basic rationale for the protocol. If the 
two patients treated in the original protocol are still immunologically deficient, then how 
will the investigators know if they succeed in repairing holes in their immune repertoire 
with the new protocol if they did not know where these holes are? Dr. Anderson 
responded that the RAC seemed to be uncomfortable with the question of what was 
happening with the present patients. Although the original protocol was designed to 
transduce peripheral blood T lymphocytes, it has to be recognized that this target cell 
population is rather heterogenous. Among the spectrum of cells are early progenitor stem 
Recombinant DNA Research, Volume 15 
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