ganisms that do not produce potent 
polypeptide toxins.! 54) 
m-C-l-a-<l)-(c>. Intact virus gen- 
omes with appropriate helper. If neces- 
sary, can be used In P3 conditions for 
shotgun experiments to propagate 
DNA sequences from eukaryotic or- 
ganisms that do not produce potent 
polypeptide toxins.! 34) 
m-C-l-a-dWd). Experiments in- 
volving the use of defective polyoma 
virus genomes to propagate DNA se- 
quences from eukaryotic viruses will 
be evaluated by NIH on a case-by-case 
basis ! 45) and will be conducted under 
the recommended physical contain- 
ment conditions. 
III-C-l-a-<2). Nonproductive Virus- 
CeU. Interactions. Defective or intact 
polyoma virus genomes can be used as 
vectors in P2 conditions to transform 
nonpermlssive cells in culture, pro- 
vided the inserted DNA sequences are 
not derived from eukaryotle viruses. In 
the latter case, such experiments will 
be evaluated by NIH on a case-by-case 
basis.!45) 
IH-C-l-b. Simian Virus 40. 
III-C-l-b-(l). Productive Viruses- 
CeU Interactions. 
m-C-l-b-aWa). SV40 DNA, ren- 
dered unconditionally defective by a 
deletion in an essential gene, with ap- 
propriate helper, can be used in P2 
conditions to propagate DNA se- 
quences from: 
III-C-l-b-<l)-!a)-!I). Bacteria of 
Class 1 or Class 2C1], or their phages 
or plasmids, except for those that pro- 
duce potent polypeptide toxins;! 34) 
m-C-l-b-<lMaM2). Uninfected Af- 
rican green monkey kidney cell cul- 
tures. 
m-C- l-b-< 1Mb). SV40 DNA, ren- 
dered unconditionally defective by a 
deletion in an essential gene, with an 
appropriate helper, can be used in P3 
conditions to propagate DNA se- 
quences from eukaryotic org anisms 
that do not produce potent polypep- 
tide toxins! 34) !shotgun experiments 
or purified DNA). 
ni-C-l-b-ilWc). Experiments in- 
volving the use of defective SV40 gen- 
omes to propagate DNA sequences 
from eukaryotic viruses will be evalu- 
ated by the NIH on a case-by-case 
basis (45) and will be conducted under 
the recommended physical contain- 
ment conditions. 
IH-C-l-b-!2). Nonproductive Virus- 
Cell Interactions. Defective or Intact 
SY40 genomes can be used as vectors 
in P2 conditions to transform nonper- 
mlssive cells in culture, provided the 
inserted DNA sequences are not de- 
rived from eukaryotic viruses. In the 
latter case, such experiments will be 
evaluated by NTH on a case-by-case 
basis.!45) 
III-C-I-c. Human Adeno- viruses 2 
and 5. 
NOTICES 
m-C-l-c-<l). Productive Virus-Cell 
Interactions. 
III-C-l-c-ClMa). Human adenovir- 
uses 2 and 5, rendered unconditionally 
defective by deletion of at least two 
capsid genes, with appropriate helper, 
can be used in P3 conditions to propa- 
gate DNA sequences from: 
m-C-l-e-flMaWI). Bacteria of 
Class 1 or Class 2[1J or their phages or 
plasmids except for those that pro- 
duce potent polypeptide toxins; (34) 
Hl-C-l-c-tlMaHl). Eukaryotic or- 
ganisms that do not produce potent 
polypeptide toxins! 34) ! shotgun ex- 
periments or purified DNAX 
III-C-I-c-< 1Mb). Experiments In- 
volving the me of unconditionally de- 
fective human adenovirus 2 and 5 gen- 
omes to propagate DNA sequences 
from eukaryotic viruses will be evalu- 
ated by NIH on a case-by-case 
basis! 45) and will be conducted under 
the recommended physical contain- 
ment conditions. 
HI-C-l-o-(2X Non-productive virus - 
cell interactions. Defective or intact 
human adenovirus 2 and 5 genomes 
can be used as vectors in P2 conditions 
to transform nonpermlssive cells in 
culture, provided the inserted DNA se- 
quences are not derived from eukaryo- 
tic viruses. In the latter case, such ex- 
periments will be evaluated by NIH on 
a case-by-case basis.! 45) 
Hl-C-l-d. Murine Adenovirus Strain 
FL. 
IH-C-l-d-!l). Productive Virus-Cell 
Interactions. 
m-C-l-d-dHa). Unconditionally 
defective murine adenovirus strain FL 
genomes, with appropriate helper, can 
be used in P2 conditions to propagate 
DNA sequences from: 
m-C-1-d-flMaMI). Bacteria of 
Class 1 or Class 2 [1] or their phages 
or plasmids except for those that pro- 
duce potent polypeptide toxins;! 34) 
III-C-l-d-!lMaM2). Eukaryotic or- 
ganisms that do not produce potent 
polypeptide toxins! 34) !shotgun ex- 
periments or purified DNA), 
IH-C-l-d-dMb). Experiments in- 
volving the use of intact murine aden- 
ovirus strain FL genomes to propagate 
DNA sequences from prokaryotic or 
eukaryotic organisms will be evaluated 
by NIH on a case-by-case basis! 45) and 
will be conducted under the recom- 
mended physical containment condi- 
tions. 
IU-C-l-d-!lMc). Experiments in- 
volving the use of unconditionally de- 
fective murine adenovirus strain FL 
genomes to propagate DNA sequences 
from eukaryotic viruses will be evalu- 
ated by NIH on a case-by-case 
basis!45) and will be conducted under 
the recommended physical contain- 
ment conditions. 
HI-C-l-d-!2). Non-Productive Virus- 
Cell Interactions. Defective or intact 
murine adenovirus strain FL genomes 
FEDERAL REGISTER, "OL 43, NO. 146— FRIDAY, JULY 2S, 
33081 
can be used as vectors in P2 conditions 
to transform nonpermlssive cells iw 
culture, provided the inserted DNA se- 
quences are not derived from eukaryo- 
tic viruses. In the latter case, such es-l 
perimenta will be evaluated by lflH Oft 
a case-by-case basis! 45). 
ni-C-l-e. All Other Potential Viral 
Vectors. 
IU-C-l-e-41). Experiments involving? 
recombinant DNA molecules contain* 
ing viral DNA segments consisting of 
25 percent or leas of the virus genome 
can be done: 
IH-C-l-edWa). Ia PI condition* 
when the recombinant DNA is to bs 
Integrated into the cell genome or 1* 
known to replicate as a plasmid ha 
cells in culture, provided the addition- 
al DNA sequences are not derived 
from a eukaryotic virus. In the latter 
case, such experiments will be evaluat- 
ed by NIH on a case-by-case basis;! 45 k 
IH-C-l-e— <lMb). Under physical 
containment conditions to be deter- 
mined by NIH! 45) when a viral helper, 
will be used to propagate DNA se- 
quences from prokaryotic or eukaryo- 
tic organisms. 
III-C-l-e-<2). Experiments Involving 
the use of other intact or defective 
virus genomes to propagate DNA se- 
quences from prokaryotic or eukaryo- 
tic organisms !and viruses), or as vec- 
tors to transform nonpermlssive cells, 
will be evaluated by NIH on a case-by- 
case basts! 45) and will be conducted 
under the recommended physical con- 
tainment conditions. 
NIH will also review all experiments 
Involving the use of virus vectors In 
animals and the physical containment 
conditions appropriate for such stud- 
ies. 
IH-C-2. Invertebrate Host-Vector 
Systems in Which Insect Viruses Are 
Used To Propagate Other DNA Seg- 
ments. As soon as Information be- 
comes available on the host range re- 
strictions and on the infectivity, per- 
sistance, and integration of the viral 
DNA in vertebrate and Invertebrate 
cells, experiments involving the use of 
Insect viruses to propagate DNA se- 
quences will be evaluated by NIH on a 
case-by-case basis! 45) and will be con- 
ducted under the recommended physi- 
cal containment conditions. Experi- 
ments should be done in established 
Invertebrate cell lines and should 
follow, where appropriate, criteria rec- 
ommended for vertebrate viral DNA 
vectors !see Section III-C-1). 
IH-C-3. Plant Viral Host-Vector Sys- 
tems. The DNA plan viruses which 
could currently serve as vectors for 
cloning genes in plants and plant cell 
protoplasts are Cauliflower Mosaic 
Virus (CaMV) and its close relatives, 
which have relaxed circular double- 
stranded DNA genomes with a molecu- 
lar weight of 4.5x10* and Bean 
Golden Mosaic Virus IBGMV) and re- 
1971 
[ 42 ] 
