Probing Sequence Variation in the Receptor-Targeting Domain of Feline Leukemia Virus Envelope Proteins with Peptide Display Libraries

Heart-targeted adeno-associated viral vectors selected by in vivo biopanning of a random viral display peptide library

“…Also, the post-entry events may be determined by yet unknown tissue-specific factors. A major step forward to improve the target peptide design has been the development of virus display peptide libraries [33][34][35][36][37] or libraries of random capsid chimeras derived from different AAV serotypes. [8][9][10] In such libraries, a multitude of potentialtargeting motifs is presented within the restrictions of capsid assembly and genome packaging.…”

Library selection and directed evolution approaches to engineering targeted viral vectors

“…Large pools of viral envelope mutants can be generated using a number of approaches, including randomly shuffling gene templates from different parent viruses , inserting random peptide sequences at a specific location Roth, 2002, 2003;Bupp et al, 2005Bupp et al, , 2006, or inserting a defined peptide into random locations Schaffer, 2006a, 2006b). The resulting envelope mutant genetic library is inserted into recombinant viral genomes, and each envelope protein mutant is packaged to generate virus particles encompassing the genome that encodes it.…”

“…Some of the earliest efforts to apply library selection approaches to target retroviral vectors involved libraries where short, random peptide sequences were genetically substituted into the receptor-determining region (RDR) of feline leukemia virus subgroup A (FeLV-A) envelope proteins followed by selection on target cells (Table I) Roth, 2002, 2003;Bupp et al, 2005Bupp et al, , 2006. In contrast to MLV envelope proteins that require changes in both variable regions of their receptor-binding domain (VRA and VRB), modification of only the VRA domains of FeLV envelope proteins allows modulation of viral tropism without severe structural perturbation (Bupp and Roth, 2002).…”

“…Subsequent work by Bupp et al (2005) demonstrated that the degree of cell specificity of the selected envelope protein variants varied depending on cell type used during the library selection. While the D17 cell-specific envelope protein variants were obtained when they used D17 cells for library selection, variants of broader tropism were isolated when AH297 feline cells were employed (Bupp et al, 2005).…”

“…While the D17 cell-specific envelope protein variants were obtained when they used D17 cells for library selection, variants of broader tropism were isolated when AH297 feline cells were employed (Bupp et al, 2005). Furthermore, a library, whose individual viral particle variants contained/displayed both the same random peptide library as well as amphotropic murine leukemia 4070A virus envelope proteins on their surfaces, yielded an interesting result after selection on 4070A-infected PC-3 human prostate cells.…”