This unexpected small increase of in vivo potency was caused by poor serum pharmacokinetics and lung bio-availability that resulted from unexpectedly broad tissue binding.
For example, the A4B4 variant, (a prototype of Motavizumab, which is an in vitro affinity matured anti-RSV mAb derived from palivizumab), demonstrated broad tissue binding and accelerated clearance in vivo (Wu et al., 2007).
The reported hydrogel-mediated gene delivery platform using biodegradable polyplexes may serve as a local depot for sustained transgene expression in situ to enhance tissue engineering across broad tissue types.
High replication efficiency, broad tissue tropism and systemic replication seem to determine the pathogenicity of H5N1 viruses in animals [3].
Transgenic mice (Tg) expressing human Trx1 (hTrx1) with added nuclear localization signal (NLS) showed broad tissue expression and nuclear localization.
This widespread increase in iNOS may be due to the fact that in chickens H5N1 strains tend to have a broad tissue tropism [8], [44], [45].
Previous studies have shown that evolutionarily conserved protein-coding genes have a broad tissue expression profile in mammals, insects, and plants [21].
Whereas most PI3Ks have a broad tissue distribution, the tyrosine kinase-linked p110δ isoform has previously been shown to be enriched in leukocytes.
In contrast to the granulocyte-restricted CEACAM3, CEACAM1 has a broad tissue distribution and is expressed on hematopoetic cells, endothelial cells and epithelial cells [31], [32].
The broad tissue distribution of PiT1 and PiT2 has led to the proposal that these transporters could play a housekeeping role for cellular Pi homeostasis [2], [7], [8].
