PMID- 16806384 OWN - NLM STAT- MEDLINE DCOM- 20061010 LR - 20141120 IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 353 IP - 1 DP - 2006 Sep 15 TI - Adeno-associated virus (AAV) capsid genes isolated from rat and mouse liver genomic DNA define two new AAV species distantly related to AAV-5. PG - 68-82 AB - Using polymerase chain reactions and genome walking strategies, adeno-associated virus (AAV)-like capsid genes were isolated from rat and mouse liver genomic DNA, where they are present at <5 copies per cell. These genes define two new species of AAVs since their amino acid sequences are <60% identical to each other or to any other AAV capsid. They are most similar to the AAV-5 and goat AAV capsids. A recombinant vector with the mouse AAV capsid and a lacZ transgene (rAAV-mo.1 lacZ) was able to transduce rodent cell lines in vitro. However, it was not able to transduce eight human cell lines or primary human fibroblasts in vitro. It did not bind heparin and its ability to transduce cells in vitro was not inhibited by heparin, mucin, or sialic acid suggesting it uses a novel entry receptor. rAAV-mo.1 lacZ was 29 times more resistant to in vitro neutralization by pooled, purified human IgG than AAV-2. In vivo, rAAV-mo.1 lacZ efficiently transduced murine ocular cells after a subretinal injection. Intramuscular injection of a rAAV-mo.1 human factor IX (hFIX) vector into mice resulted in no detectable hFIX in plasma, but intravenous injection resulted in high plasma levels of hFIX, equivalent to that obtained from a rAAV-8 hFIX vector. Biodistribution analysis showed that rAAV-mo.1 primarily transduced liver after an intravenous injection. These AAV capsids may be useful for gene transfer in rodents. FAU - Lochrie, Michael A AU - Lochrie MA AD - Avigen, Inc., 1301 Harbor Bay Parkway, Alameda, CA 94502-6541, USA. mlochrie@synergenics.net FAU - Tatsuno, Gwen P AU - Tatsuno GP FAU - Arbetman, Alejandra E AU - Arbetman AE FAU - Jones, Kris AU - Jones K FAU - Pater, Cheryl AU - Pater C FAU - Smith, Peter H AU - Smith PH FAU - McDonnell, Jennifer W AU - McDonnell JW FAU - Zhou, Shang-Zhen AU - Zhou SZ FAU - Kachi, Shu AU - Kachi S FAU - Kachi, Michiko AU - Kachi M FAU - Campochiaro, Peter A AU - Campochiaro PA FAU - Pierce, Glenn F AU - Pierce GF FAU - Colosi, Peter AU - Colosi P LA - eng GR - EY12609/EY/NEI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060630 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (DNA, Viral) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Capsid/chemistry/*physiology MH - Cell Line MH - Cell Line, Tumor MH - Conserved Sequence MH - DNA, Viral/genetics/*isolation & purification MH - Dependovirus/chemistry/*genetics MH - Gene Dosage MH - HeLa Cells MH - Humans MH - In Vitro Techniques MH - Liver/*virology MH - Mice MH - Models, Molecular MH - Molecular Sequence Data MH - NIH 3T3 Cells MH - Neutralization Tests MH - Protein Structure, Tertiary MH - Rats MH - Sequence Homology, Amino Acid MH - Species Specificity MH - Tissue Distribution MH - Transduction, Genetic EDAT- 2006/06/30 09:00 MHDA- 2006/10/13 09:00 CRDT- 2006/06/30 09:00 PHST- 2006/02/26 00:00 [received] PHST- 2006/04/24 00:00 [revised] PHST- 2006/05/18 00:00 [accepted] PHST- 2006/06/30 09:00 [pubmed] PHST- 2006/10/13 09:00 [medline] PHST- 2006/06/30 09:00 [entrez] AID - S0042-6822(06)00354-0 [pii] AID - 10.1016/j.virol.2006.05.023 [doi] PST - ppublish SO - Virology. 2006 Sep 15;353(1):68-82. doi: 10.1016/j.virol.2006.05.023. Epub 2006 Jun 30.