I'm currently doing a bunch of Regex replaces like this
_skeleton = Regex.Replace(_skeleton, "&%currTIME", DateTime.Now.ToString());
Is there any way to make it so I don't have to write '_skeleton ='?
Maybe using 'out'?
Since strings are immutable, you cannot change their contents. You must create a new string with the contents you want.
Think of it like any other immutable type (DateTime, int, etc.)
int i = 1;
i++; // i = i + 1
i += 2; // i = i + 2
DateTime d = DateTime.Now
d = d.AddDays(1);
string s = "s";
s = s + "tring";
You can wrap the functionality to be a little more functional in nature:
public void MyRegexReplace(ref string mystring, string pattern, string replaceWith)
{
    mystring = Regex.Replace(mystring, pattern, replaceWith);
}
And then call it like:
MyRegexReplace(ref _skeleton, "&%currTIME", DateTime.Now.ToString());
But this doesn't seem that useful to me.
mystring as a ref parameter :/If you don't want to have to keep repeating yourself for multiple replacements on the same string, you can nest the calls to Regex.Replace():
_skeleton = Regex.Replace(
                    Regex.Replace(_skeleton, "foo", "bar"),
            "&%currTIME", DateTime.Now.ToString());
(Editing the answer because my response is too long for a comment)
You don't need to even indent them:
_skeleton = Regex.Replace(Regex.Replace(Regex.Replace/*...*/(_skeleton,
            "foo", "bar"),
            "baz", "blaz"),
            //..
            "TIMTOWTDI", "There Is More Than One Way To Do It"
            ));