Abstract: A lipid comprising a tri-chain cation having a cationic head group and three or more C7-24 hydrocarbyl groups for use in non-viral gene delivery systems, for example in the formation of lipopolyplex transfection vectors. Exceptionally good nucleic acid transfection is observed when nucleic acid and targeting peptides are formulated with the lipid of the invention (or lipid formulated with a co-lipid) into a LPD complex.

Abstract: A ribonucleoprotein (RNP) delivery system comprising (a) a cationic lipid; (b) a phospholipid; (c) a peptide of the structure A-B-C in which A is a polycationic nucleic acid-binding component, B is a spacer element comprising two or more amino acid residues, and C is a cell surface receptor binding component; and (d) a ribonucleoprotein (RNP) complex comprising a CRISPR-associated protein and guide RNA, pharmaceutical compositions comprising such a ribonucleoprotein (RNP) delivery system, and methods for the treatment or prophylaxis of a condition caused in a human or in a non-human animal by a defect and/or a deficiency in a gene, or for RNA therapy, or for the treatment of a cancer, which comprises administering the RNP delivery system or pharmaceutical composition to the human or to the non-human animal.

Abstract: A liposome comprising a cationic lipid, a phospholipid and a peptide and optionally consisting of from 20 to 50% by molarity cholesterol, based on the total amount of lipids, for use in non-viral gene delivery systems, for example, in the formation of lipopolyplex transfection vectors for the delivery of mRNA to cells.

Abstract: A lipid comprising a tri-chain cation having a cationic head group and three or more C7-24 hydrocarbyl groups for use in non-viral gene delivery systems, for example in the formation of lipopolyplex transfection vectors. Exceptionally good nucleic acid transfection is observed when nucleic acid and targeting peptides are formulated with the lipid of the invention (or lipid formulated with a co-lipid) into a LPD complex.

Abstract: The invention provides a peptide derivative of formula A-B-C wherein A is a polycationic nucleic acid-binding component; B is a spacer element peptide that is susceptible to cleavage within a cell; and C is a cell surface receptor binding component. The invention also provides a lipid derivative of general formula (I): (PEG)q-Linker-Spacer-Cationic headgroup-carbon skeleton-(hydrophobic chain)o wherein: the Linker is a group susceptible to cleavage within a cell; the Spacer is a group linking the Linker to the Cationic headgroup; q denotes the number of PEG chains and q=1, 2 or 3; o denotes the number of hydrophobic chains and o=1, 2 or 3; the carbon skeleton is a group linking the hydrophobic chains to the cationic headgroup. The peptide and lipid derivatives find use in non-viral gene delivery systems.

Abstract: The invention provides a peptide having at least 3 amino acids comprising an amino acid sequence selected from a) X1SM [SEQ.ID.NO.: 1] b) LX2HK [SEQ.ID.NO.: 2] c) PSGX3ARA [SEQ.ID.NO.: 9] d) SX4RSMNF [SEQ.ID.NO.: 16] e) LX5HKSMP [SEQ.ID.NO.: 18] in which X1 is a basic amino acid residue, X2 is Q or P, X3 is A or T, X4 is an acidic amino acid residue and X5 is P or Q. The invention further provides non-viral cell-targeting vector complexes and methods associated therewith.

Abstract: A peptide consisting of or comprising an amino acid sequence selected from a) PX1X2X3T [SEQ.ID.NO.:1]; b) PSX4S [SEQ.ID.NO.:2]; c) QX5X6X7Q [SEQ.ID.NO.:3]; d) SX8S [SEQ.ID.NO.:4], in which X1, X2 and X3, which may be the same or different, each represents an amino acid residue; X4 represents an amino acid residue; and X5 and X7, which may be the same or different, each represents an amino acid residue, X6 represents an amino acid residue having an amide side chain; and X8 represent an amino acid having an aliphatic side chain, which peptide binds to dendritic cells and also to other types of cells. The peptide may be used a target non-viral and viral vectors to such cells.

Abstract: The invention provides a peptide derivative of formula A-B-C wherein A is a polycationic nucleic acid-binding component; B is a spacer element peptide that is susceptible to cleavage within a cell; and C is a cell surface receptor binding component. The invention also provides a lipid derivative of general formula (I): (PEG)q-Linker-Spacer-Cationic headgroup-carbon skeleton-(hydrophobic chain)o wherein: the Linker is a group susceptible to cleavage within a cell; the Spacer is a group linking the Linker to the Cationic headgroup; q denotes the number of PEG chains and q=1, 2 or 3; o denotes the number of hydrophobic chains and o=1, 2 or 3; the carbon skeleton is a group linking the hydrophobic chains to the cationic headgroup. The peptide and lipid derivatives find use in non-viral gene delivery systems.

Abstract: The invention provides a peptide having at least 3 amino acids comprising an amino acid sequence selected from a) X1SM [SEQ.ID.NO.: 1] b) LX2HK [SEQ.ID.NO.: 2] c) PSGX3ARA [SEQ.ID.NO.: 9] d) SX4RSMNF [SEQ.ID.NO.: 16] e) LX5HKSMP [SEQ.ID.NO.: 18] in which X1 is a basic amino acid residue, X2 is Q or P, X3 is A or T, X4 is an acidic amino acid residue and X5 is P or Q. The invention further provides non-viral cell-targeting vector complexes and methods associated therewith.

Abstract: The invention provides a peptide having at least 3 amino acids comprising an amino acid sequence selected from a) X1SM [SEQ.ID.NO.: 1] b) LX2HK [SEQ.ID.NO.: 2] c) PSGX3ARA [SEQ.ID.NO.: 9] d) SX4RSMNF [SEQ.ID.NO.: 16] e) LX5HKSMP [SEQ.ID.NO.: 18] in which X1 is a basic amino acid residue, X2 is Q or P, X3 is A or T, X4 is an acidic amino acid residue and X5 is P or Q. The invention further provides non-viral cell-targeting vector complexes and methods associated therewith.

Abstract: A peptide consisting of or comprising an amino acid sequence selected from a ) Px1X2X3 T [SEQ.ID.NO.:11]; b) PSX4S [SEQ.ID.NO.:2]; C) QX5X6X7Q [SEQ.ID.NO.:3]; d) SX8S [SEQ-ID.NO.:4], in which X1, X2 and X3, which may be the same or different, each represents an amino acid residue; X4 represents an amino acid residue; and x 5 and X7, which may be the same or different, each represents an amino acid residue, X6 represents an amino acid residue having an amide side chain; and X8 represent an amino acid having an aliphatic side chain, which peptide binds to dendritic cells and also to other types of cells. The peptide may be used a target non-viral and viral vectors to such cells.

Abstract: The invention provides a peptide having at least 3 amino acids comprising an amino acid sequence selected from a) X1SM [SEQ.ID.NO.: 1] b) LX2HK [SEQ.ID.NO.: 2] c) PSGX3ARA [SEQ.ID.NO.: 9] d) SX4RSMNF [SEQ.ID.NO.: 16] e) LX5HKSMP [SEQ.ID.NO.: 18] in which X1 is a basic amino acid residue, X2 is Q or P, X3 is A or T, X4 is an acidic amino acid residue and X5 is P or Q. The invention further provides non-viral cell-targeting vector complexes and methods associated therewith.

Abstract: The invention provides a peptide having at least 3 amino acids comprising an amino acid sequence selected from a) X1SM [SEQ.ID.NO.:1] b) LX2HK [SEQ.ID.NO.:2] c) PSGX3ARA [SEQ.ID.NO.:9] d) SX4RSMNF [SEQ.ID. NO.:16] e) LX5HKSMP [SEQ.ID.NO.:18] in which X is a basic amino acid residue, X1 is Q or P, X2 is A or T, X3 is an acidic amino acid residue and X4 is P or Q, the invention further provides non-viral cell-targeting vector complexes and methods associated therewith.

Abstract: The invention provides a peptide having at least 3 amino acids comprising an amino acid sequence selected from a) X1SM [SEQ.ID.NO.:1] b) LX2HK [SEQ.ID.NO.:2] c) PSGX3ARA [SEQ.ID.NO.:9] d) SX4RSMNF [SEQ.ID. NO:16] e) LX5HKSMP [SEQ.ID.NO.:18] in which X is a basic amino acid residue, X1 is Q or P, X2 is A or T, X3 is an acidic amino acid residue and X4 is P or Q, the invention further provides non-viral cell-targeting vector complexes and methods associated therewith.

Abstract: Transfection of confluent cells or other slowly dividing or non-dividing cells that are in contact with each other with a nucleic acid using a non-viral receptor targeted vector may be improved by the concurrent use of an agent that disrupts cell-cell junctions, especially EGTA. The vector is especially an integrin-targeting transfection vector complex comprising (i) a nucleic acid, especially a nucleic acid encoding a sequence of interest, (ii) an integrin-binding component, especially an integrin-targeting peptide, (iii) a polycationic nucleic acid-binding component, especially an oligolysine, and (iv) a lipid component, especially, DOPE, DOTMA, DOSPA or combinations thereof. Various applications of the improved method of transfection are described.